Bone metastasis is common for breast cancer and associated with poor prognosis. Currently, radiotherapy (RT) serves as the standard treatment for patients exhibiting symptoms of bone metastasis to alleviate pain. Whether earlier application of RT will better control bone metastasis remains unclear.

We utilized a mouse model of breast cancer bone metastasis by intra-femoral injection of 4T1-luc breast tumor cells. The bone metastasis was treated by RT using various doses, timings, and modalities. Tumor growth was assessed through bioluminescence imaging, and lung metastases was quantified following lung tissue fixation. Flow cytometry was employed to analyze alterations in immune cell populations.

Single high-dose RT suppressed tumor growth of bone metastases, but caused severe side effects. Conversely, fractionated RT mitigated tumor growth in bone metastases with fewer adverse effects. Fractioned RT initiated at the early stage of bone metastasis effectively inhibited tumor growth in the bone, suppressed secondary lung metastases, and prolonged mouse survival. In line with the known pro- and anti-metastatic effects of neutrophils and T cells in breast cancer, respectively, earlier fractioned RT consistently decreased the proportions of neutrophils while increased the proportions of T cells in both the bone and the lung tissues.

The data suggest that fractionated RT can inhibit the progression of early stage of bone metastasis and reduce secondary lung metastasis, leading to favorable outcomes. Therefore, these findings provide preclinical evidence to support the application of fractionated RT to treat patients with bone metastasis as earlier as possible.

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally and the second leading cause of cancer-related mortality. This study investigates the diagnostic value of peripheral blood inflammatory indices, including the Cancer-Inflammation Prognostic Index (CIPI), Systemic Inflammation Response Index (SIRI), Hemoglobin-Albumin-Lymphocyte-Platelet (HALP) index, Neutrophil-to-Lymphocyte Ratio (NLR), and Platelet-to-Lymphocyte Ratio (PLR), in the early diagnosis of clinicopathological characteristics of CRC.

This retrospective observational study involved 224 patients with CRC aged over 45, admitted to Rasoul-Akram Hospital from September 2019 to 2023, undergoing elective CRC surgery. Key demographic and clinicopathological data were collected alongside blood samples to derive inflammatory indices. Univariate and multivariate analyses were applied to determine metastasis and stage predictors. A receiver operating characteristic (ROC) analysis was performed to evaluate the SIRI diagnostic value in differentiating tumors with and without metastasis and the CIPI diagnostic value in differentiating tumors with high and low stage.

The study identified a significant association between elevated SIRI levels and metastasis in univariate analysis (OR = 2.79, CI = 1.12-6.94). Multivariate analysis shows CIPI is associated with advanced tumor stages (OR = 1.97, CI = 1.14-3.38). According to the ROC curve, the optimal cut-off value of SIRI and CIPI was 1.376 (sensitivity 52.6%, specificity 60.8%, AUC = 61.5%) for diagnosing the metastasis and 7.114 (sensitivity 59.8%, specificity 57%, AUC = 57.9%) for diagnosing the tumor stage, respectively.

The findings show that a higher SIRI value is associated with a higher chance of metastasis and a higher CIPI value is associated with a higher chance of advanced stages. Furthermore, the study advocates for the integration of these inflammatory indices into clinical practice to facilitate personalized treatment strategies and early diagnosis, enhancing the prognosis and survival in CRC.

Cancer-associated fibroblasts (CAFs) represent a central cell population of the tumor microenvironment (TME). Recently, single-cell RNA-sequencing (scRNA-seq) analyses of primary tumors of different cancer entities yielded different classifications of CAF subsets underscoring the heterogeneity of CAFs within the TME. Here, we analyzed the transcriptional signatures of approximately 8400 CAFs and normal fibroblasts by scRNA-seq and compared genetic profiles of CAFs from murine melanoma primary tumors to CAFs from corresponding melanoma lung metastases. This revealed distinct subsets for primary tumor and metastasis-specific CAF populations, respectively. Combined with the spatial characterization of metastasis CAFs at the RNA and protein level, scRNA analyses indicate tumor-dependent crosstalk between neutrophils and CAFs, mediated via SAA3 and IL1b-related signaling pathways, which can be recapitulated in vitro. Analyzing tissue sections of human patient samples, this interaction was found to be present in human melanoma metastasis. Taken together, our data highlight unique characteristics of metastasis CAFs with potential therapeutic impact for melanoma metastasis.

Current studies found that the peritumoral tissue of hepatocellular carcinoma (HCC) may be different from normal liver tissue based on proteomics, and related to progression, recurrence and metastasis of HCC. Our previous study proposed "peritumor microenvironment (PME)" to summarize the influence of peritumor tissue on occurrence and progression of HCC. Peritumor CYP2E1 activity was significantly elevated in HCC, and related to occurrence and progression of HCC. However, the effectiveness and mechanism of inhibiting CYP2E1 against HCC remain unclear. In this study, by integrating the advantages of proteomics and transcriptomics, we reanalyzed the various influencing factors in PME. Although there were large differences in the occurrence and progression, the immunity and inflammation still played crucial roles. Peritumor neutrophil were "pro-tumor" phenotype in the stage of progression, while it showed cytotoxicity for tumor cell in the occurrence stage. CYP2E1 activity is associated with peritumor neutrophil infiltration and occurrence of HCC. CYP2E1 inhibitor Q11 showed anti-tumor effects in an orthotopic HCC mouse model by promoting secretion of chemokines and infiltration of neutrophils in peritumor tissue. Overall, these findings provided a reasonable mechanism of anti-tumor effects of CYP2E1 inhibitors, which may be a new strategy for the prevention and treatment of HCC.

RNA methylation is a potential target for cancer therapy, while anoikis, a form of programmed cell death, is linked to cancer metastasis. However, the prognostic and immune significance of RNA methylation- and anoikis-related genes in colorectal cancer (CRC) remains unknown.

Transcriptomic and clinicopathological data for CRC were obtained from TCGA and the GEO databases. A novel signature was constructed based on RNA methylation- and anoikis-related genes using univariate and multivariate Cox regression as well as LASSO Cox regression methods. CRC patients were stratified into low- and high-risk groups based on this signature. Differences in prognosis, immune infiltration, and drug sensitivity between two groups were analyzed. Finally, immunohistochemistry, western blot, and RT-qPCR were employed to validate the expression of the key gene SERPINE1 in CRC tissues and cells, as well as the effect of FTO on its expression.

We identified 79 differentially expressed RNA methylation-associated anoikis-related genes (RMRARGs) in both cancerous and normal tissues. A signature composed of 9 key genes (BID, FASN, PLK1, CDKN3, MYC, EPHA2, SERPINE1, CD36, PDK4) was established. Kaplan-Meier analysis revealed a poorer prognosis in the high-risk group. Compared to the other three published models, this signature demonstrated superior predictive performance based on the ROC curve analysis. Functional analyses highlighted differences in drug sensitivities and signaling pathways between risk groups. Furthermore, immune analysis results showed that risk score was associated with some immune cells and immune checkpoints. Immunohistochemistry showed high SERPINE1 expression in CRC tissues, with FTO expression positively correlated with SERPINE1. Furthermore, RT-qPCR and western blot indicated FTO knockdown markedly downregulated SERPINE1 levels.

Our findings underscore the prognostic value of this signature in CRC patients and its utility in assessing immune status. Additionally, the m6A demethylase FTO regulates the expression of the anoikis-related gene SERPINE1.

Pancreatic cancer liver metastasis is an important factor leading to dismal prognoses. The details of adaptive immune remodeling in liver metastasis, especially the role of neutrophils, remain elusive. Here, combined single-cell sequencing with spatial transcriptomics results revealed that liver metastases exhibit more aggressive transcriptional characteristics and higher levels of immunosuppression compared with the primary tumor. We identified neutrophils_S100A12 (S100 calcium binding protein A12) cells as the pivotal pro-metastatic cluster, specifically distributed at the invasive front of the metastatic lesions. Mechanistically, our findings indicated that nuclear factor erythroid 2 (NFE2) is a key transcription factor regulating neutrophil phenotypic polarization. Metastatic tumors produce transforming growth factor β to activate the SMAD3 pathway within neutrophils, inducing NFE2-driven polarization. NFE2 promotes the transcription of peptidylarginine deiminase 4 by binding to its promoter, leading to the generation of neutrophil extracellular traps at the invasive front. Collectively, our data demonstrate that NFE2-driven neutrophil polarization is a potential target for anti-metastatic therapy.

Primary liver cancers (PLCs) remain a major challenge to global health and an escalating threat to human life, with a growing incidence worldwide. PLCs are composed of hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and mixed HCC-CCA, accounting for 85 %, 10 %, and 5 % of cases, respectively. Among the numerous identified risk factors associated with liver cancers, Alpha 1-AntiTrypsin Deficiency (AATD) genetic disease emerges as an intriguing one. AATD-related liver disease may lead to chronic hepatitis, cirrhosis, and PLCs in adulthood. Although our knowledge about the natural history of AATD-liver disease has improved recently, liver cancers associated with AATD remain poorly understood and explored, while this specific population is at a 20 to 50 times higher risk of developing PLC. Thus, we review here current knowledge about AATD-associated PLCs, describing the impact of AATD genotypes on their occurrence. We also discuss emerging hypotheses regarding the AATD PiZZ genotype-related hepatic carcinogenesis process. Finally, we perform an updated analysis of the United Kingdom Biobank database that highlights and confirms AATD PiZZ genotype as an important HCC risk factor.

Gastric cancer is one of the most frequent malignancies and a serious concern in the global public health realm. Neutrophils, the most numerous myeloid cells in human blood, are emerging as significant regulatory variables in cancer. This study examines the molecular processes behind the link between gastric cancer's malignant character and neutrophils in the disease. This study aims to reveal the role of P2RX1 in neutrophils in gastric cancer and investigate its effects on the migration, invasion, and apoptosis of gastric cancer cells, with the hope of providing new targets and strategies for the treatment of gastric cancer. P2RX1 expression levels in gastric cancer samples were examined using The Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD). The signal pathways enriched by P2RX1-related differential gene expression were examined using GSEA. P2RX1 mRNA levels were examined using qPCR. Jak/Stat signaling pathway-related proteins and P2RX1 expression levels were subjected to western blot analysis. The apoptotic rate, migration, invasion, and cell viability were evaluated using flow cytometry, Transwell, and CCK-8 tests. Immunohistochemistry was used to detect the expression of P2RX1 in tumor tissues. Neutrophils and P2RX1 were both underexpressed in gastric cancer. In gastric cancer neutrophils, overexpression of P2RX1 increased cancer cell apoptosis while suppressing migration, invasion, and viability of the cells. Jak/Stat signaling pathway was connected to production of neutrophil P2RX1, and P2RX1 overexpression could trigger the pathway in vivo and in vitro. By activating its own Jak/Stat signaling pathway, overexpression of P2RX1 in gastric cancer neutrophils improved neutrophil survival, which in turn suppressed the migration, invasion, and viability of gastric cancer cells and raised their apoptosis rate. This suggests that P2RX1 may play a significant anti-tumor role in the tumor microenvironment of gastric cancer, indicating its value as a potential therapeutic target.

The ubiquitously expressed transmembrane protein, Herpesvirus Entry Mediator (HVEM), functions as a molecular switch, capable of both activating and inhibiting the immune response depending on its interacting ligands. HVEM-Fc is a novel recombinant fusion protein with the potential to eradicate tumor cells.

The anti-tumor efficacy of HVEM-Fc was evaluated in C57BL/6 mice-bearing lung cancer models: a syngeneic model and an orthotopic model of mouse lung cancer. Additionally, patient-derived organoids were employed in conjunction with T cell co-culture systems. To investigate the underlying mechanisms, a comprehensive array of techniques was utilized, including single-cell RNA sequencing, spatial transcriptomics, bulk RNA sequencing, and flow cytometry. Furthermore, the anti-tumor effects of HVEM-Fc in combination with Programmed Death-1 (PD-1) inhibitors were assessed. Finally, mouse immune cell depletion antibodies were used to elucidate the underlying mechanisms of action.

In vivo, 1 mg/kg HVEM-Fc demonstrated effective inhibition of tumor growth and metastasis in C57BL/6 mice bearing lung cancer model and a KP orthotopic model of mouse lung cancer. Multi-omics analysis showed that HVEM-Fc induced an immune-stimulatory microenvironment. Notably, the combination of HVEM-Fc with a PD-1 inhibitor demonstrated the most potent inhibition of tumor cell growth. In vitro, HVEM-Fc was validated to eradicate tumor cells through the activation of T cells in both non-small cell lung cancer (NSCLC) organoids and T cell co-culture models.

Our data demonstrate that HVEM-Fc exerts a strong signal that augments and prolongs T-cell activity in both murine models and human NSCLC organoid models. Moreover, the combination of HVEM-Fc with a PD-1 inhibitor yields the most effective anti-tumor outcomes.

This study aimed to investigate the prognostic value of inflammation markers for advanced pulmonary lymphoepithelioma-like carcinoma (PLELC) and develop an effective prognostic model based on inflammation markers to predict the overall survival (OS) of this population.

Cox regression analysis was performed on 18 clinical and inflammation features, and a nomogram was created to predict overall survival (OS). The nomogram was evaluated by the concordance index (C-index), the time-dependent area under the receiver operating (ROC) curves (AUCs), calibration curves, and Decision Curve Analysis (DCA).

This study included a training cohort (n = 177) and a validation cohort (n = 77). The following variables were found to be independent prognostic factors for OS and used in the nomogram: Hepatitis B virus surface antigen status, gender, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein-to-albumin ratio (CAR). The C-indexes of the nomogram in the training and validation cohort were 0.740 (95% CI: 0.706-0.747) and 0.733 (95% CI: 0.678-0.788), respectively. Furthermore, time-dependent AUCs and well-fitted calibration curves showed good discriminative ability in both cohorts. Additionally, among the subset of EBV DNA data (n = 111), both ROC curve and DCA curve analysis demonstrated that the nomogram plus EBV DNA provided superior predictive performance compared to EBV DNA or the nomogram alone. Patients who received chemoimmunotherapy as the first-line treatment had better OS (not reached vs 44.4 months, P = 0.015) than those with chemotherapy alone and those who received immunotherapy at any line had better OS than those who never received it (not reached vs 31.0 months, P < 0.001).

This study established and validated a prognostic nomogram model for patients with advanced PLELC. Combining the nomogram with EBV DNA more effectively predicted the prognosis of patients than the nomogram alone. Immunotherapy was found to be a critical treatment option for PLELC.

The role of the human microbiome in cancer has been extensively studied, focusing mainly on bacteria-host interactions and their impact on tumor development and treatment response. However, fungi, an immune-active component of the human microbiome, have received less attention regarding their roles in cancer. Recent studies have identified the widespread and specific colonization and distribution of fungi in multiple sites in patients across various cancer types. Importantly, host-fungal immune interactions significantly influence immune regulation within the tumor microenvironment. The rapid advancement of immune-checkpoint blockade (ICB)-based cancer immunotherapy creates an urgent need for effective biomarkers and synergistic therapeutic targets. Cancer-associated fungi and their associated antifungal immunity demonstrate significant potential and efficacy in enhancing cancer immunotherapy. This review summarizes and discusses the growing evidence of the functions and mechanisms of commensal and pathogenic cancer-associated fungi in cancer immunotherapy. Additionally, we emphasize the potential of fungi as predictive biomarkers and therapeutic targets in cancer immunotherapy.

Esophageal cancer (EC) is associated with a high morbidity and mortality rate. Immunotherapy has demonstrated effective antitumor activity in patients with EC, making it imperative to investigate easily accessible prognostic factors. Consequently, we conducted a meta-analysis to explore the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in EC patients treated with immunotherapy.

The literature search was conducted across three databases: PubMed, Embase, and Web of Science. The primary deadline for literature retrieval was July 2024. Hazard ratio (HR) with a 95% confidence interval (CI) was utilized to assess the association between NLR or PLR and overall survival (OS) as well as progression-free survival (PFS). Statistical analysis was performed using Review Manager version 5.4 and STATA version 15.0.

The meta-analysis included a total of 16 studies involving 1,481 patients. The results indicated a significant correlation between high pretreatment NLR and poor PFS (HR=1.76, 95%CI:1.38-2.25, p<0.001) as well as poor OS (HR=2.61,95%CI:1.86-3.67, p<0.001). Subgroup analyses based on tumor stage revealed that the association between elevated NLR and poor PFS was only observed in advanced EC patients. Regarding PLR, an increased PLR was found to be indicative of inferior PFS (HR=1.44, 95%CI: 1.20-1.72, p<0.001) and OS (HR=1.72,95%CI:1.08-2.74, p=0.020). However, the sensitivity analyses suggested that the observed increase in PLR lack robustness in terms of its impact on inferior OS.

Elevated NLR and PLR are associated with inferior PFS and OS in EC patients receiving immunotherapy. These findings suggest that NLR and PLR levels hold promise as prognostic biomarkers in clinical practice, offering valuable guidance for personalized immunotherapy strategies.

PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42024596737.

Objective: To evaluate the prognostic value of pre-therapeutic inflammatory markers before transarterial chemoembolization with degradable starch microspheres (DSM-TACE) in the treatment of hepatocellular carcinoma (HCC). Methods: A total of 155 patients (81% male, median age: 68 years) who underwent first-time DSM-TACE between 07/13 and 06/22 were included in the study. Inflammatory indices were dichotomized using median values. Cox proportional hazard model for univariate (UVA) and multivariate (MVA) analyses (hazard ratio; 95% CI, p-value) and Kaplan-Meier analyses (overall survival (OS) in months; 95% CI; log-rank test) were performed. Results: The median OS of the study cohort was 15.9 (12.9-20) months with a median survival according to BCLC stages A (12%), B (41%), and C (47%) of median not reached, 19.3 (15.3-27), and 7.2 (4.5-9.0) months, respectively (p < 0.0001). In the UVA, several inflammatory markers on OS were statistically significant with the systemic inflammatory response index (SIRI; ≤median (2.04) HR: 0.41 (0.19-0.89); p = 0.024) and the lymphocyte to monocyte ratio (LMR; >median (1.82) HR: 0.44 (0.2-0.9); p = 0.025) remaining statistically significant in MVA together with the BCLC stage (p = 0.0001), ALBI grade (p = 0.016), hepatic tumor burden (≤25% vs. >25%; p = 0.006), and largest HCC lesion (≤5.5 cm vs. >5.5 cm; p = 0.008). In subgroup analysis, patients with elevated LMR and reduced SIRI exhibited significantly prolonged overall survival (OS) in both BCLC B (p < 0.0001) and Child-Pugh A (p = 0.021) subgroups. Conclusion: The findings suggest that SIRI and LMR may serve as valuable tools in identifying BCLC B and Child-Pugh A patients who could potentially benefit better from DSM-TACE treatment. Nevertheless, further research is recommended to confirm these findings and to provide more comprehensive insights.

BACKGROUND Globally, esophageal cancer ranks as the sixth leading cause of cancer-related mortality. This retrospective study from a single center in Turkey aimed to evaluate hematological inflammatory biomarkers in complete blood count (CBC) data and outcomes in 113 patients with advanced esophageal carcinomas. MATERIAL AND METHODS We conducted a retrospective analysis of 113 patients with metastatic esophageal cancer composed of squamous (92), adenocarcinoma (18), and small cell (3) histology. We investigated neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet lymphocyte ratio (NLPR), neutrophile-to-monocyte ratio (NMR), systemic inflammation index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI) in terms of prognosis. RESULTS The initial treatment for 25.7% of patients consisted of a carboplatin-paclitaxel combination. In response to the initial round of chemotherapy, 52.2% of patients showed improvement (15% complete, 37.2% partial), while 18.6% experienced disease progression. Neutropenia was observed as the most prevalent severe (grades 3-4) adverse reaction, affecting 19.8% of patients. Higher NLR, PLR, SII, NLPR, SIRI, and AISI values were associated with worse survival (P=0.016, P=0.008, P=0.011, P=0.028, P=0.014, P=0.001, respectively), whereas higher LMR was correlated with better survival (P=0.001). The NMR analysis showed no significant association (P=0.46). Multivariate analysis identified independent prognostic factors except histology, PLR, and NLPR. CONCLUSIONS Research indicates that inflammatory indicators obtained from complete blood count analyses possess prognostic significance for individuals with metastatic esophageal cancer. These biomarkers demonstrate diverse capacities in forecasting the course of the disease. These simple and inexpensive markers need further confirmation to guide individualized treatment planning.

Tumor necrosis factor (TNF) has been recognized as an immune activation factor in tumor immunotherapy. Our study demonstrated that TNF blockade markedly enhanced the antitumor efficacy of oncolytic adenovirus (AdV) therapy. To minimize systemic side effects, we engineered a recombinant oncolytic AdV encoding a TNF inhibitor (AdV-TNFi) to confine TNF blockade within the tumor microenvironment (TME). AdV-TNFi significantly improved therapeutic outcomes across various solid tumor models, including four murine and two golden hamster cancers. Immune cell profiling identified CD8+ T cells as the primary mediators of AdV-TNFi-induced antitumor effects, rather than CD4+ T or NK cells. Additionally, AdV-TNFi significantly decreased the infiltration of suppressive myeloid-derived immune cells within the TME and promoted long-term antitumor immune surveillance. Further investigation indicated that TNFR2, more than TNFR1, is pertinent to the immunosuppressive TME, with a recombinant AdV-encoding anti-TNFR2 demonstrating comparable antitumor efficacy to AdV-TNFi. Moreover, AdV-TNFi enhanced the antitumor efficacy of gemcitabine and immune checkpoint blockades (ICBs), such as anti-PD-L1 and anti-TIGIT antibodies, in pancreatic carcinoma and the anti-EGFR antibody in colon carcinoma. In conclusion, intratumoral blockade of the TNF/TNFR2 axis using AdV augments cancer immunotherapy efficacy while mitigating the risks associated with systemic TNF or TNFR2 suppression, warranting further clinical investigation.

The prognostic value of the systemic immune-inflammation index (SII) for prostate cancer (PCa) patients receiving different treatments remains unclear. This research examined the relevance of SII in individuals undergoing radical prostatectomy (RP).

PubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI) dat3 abases were used to search literature up to May 2024. The quality was evaluated with Newcastle-Ottawa Scale. Outcomes examined were associations between SII and overall survival (OS), biochemical recurrence-free survival (BFS), and cancer-specific survival (CSS). Pooled analysis, Egger's test, and sensitivity analysis were conducted using Review Manager 5.4.1 and Stata 15.1. The GRADE system was employed to evaluate and grade the evidence for each outcome. Subgroup analyses were performed for outcomes with significant heterogeneity to evaluate the possible confounders, if data were sufficient.

Out of 101 identified studies, eight studies involving 8,267 individuals were included. Patients with higher SII had shorter overall survival (HR: 1.89; 95% CI: 1.31-2.71; P = 0.0006), biochemical recurrence-free survival (HR: 1.55; 95% CI: 1.08-2.22; P = 0.02), and cancer-specific survival (HR: 3.63; 95% CI: 1.66-7.94; P = 0.001). The evidence for OS and CSS was rated very low-quality due to serious heterogeneity and/or imprecision. The prognostic value of SII for BFS was rated as low-quality evidence, given no serious risk observed. Subgroup analysis showed that, except for the subgroup aged >65 years (HR: 3.70; 95%CI: 0.91, 15.06, P=0.07), the prognostic value of SII for OS was not significant, but the prognostic value of SII for OS in other subgroups was still significant.

High SII was linked to shorter OS, BFS, and CSS in patients undergoing RP. However, the quality of the evidence provided by this study was low.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024558431.

Design and development of efficient drug delivery technologies that impart site-specificity is the need of the hour for the effective treatment of lung cancer. The emergence of materials science and nanotechnology partially helped drug delivery scientists to achieve this objective. Various stimuli-responsive materials that undergo degradation at the pathological tumor microenvironment (TME) have been developed and explored for drug delivery applications using nanotechnological approaches. Nanoparticles (NPs), owing to their small size and high surface area to volume ratio, demonstrated enhanced cellular internalization, permeation, and retention at the tumor site. Such passive accumulation of stimuli-responsive materials helped to achieve spatiotemporally controlled and targeted drug delivery within the tumors. In this review, we discussed various stimuli-physical (interstitial pressure, temperature, and stiffness), chemical (pH, hypoxia, oxidative stress, and redox state), and biological (receptor expression, efflux transporters, immune cells, and their receptors or ligands)-that are characteristic to the TME. We mentioned an array of biomaterials-based nanoparticulate delivery systems that respond to these stimuli and control drug release at the TME. Further, we discussed nanoparticle-based combinatorial drug delivery strategies. Finally, we presented our perspectives on challenges related to scale-up, clinical translation, and regulatory approvals.

Gastric cancer (GC) is one of the deadly malignancies of the gastrointestinal tract. Research has confirmed the linkage of P2RX1 with immune cell activation and tumor progression. This project focused on the impact of P2RX1 level in neutrophils on the efficacy of immune checkpoint inhibitor (ICI) treatment in GC.

Blood samples from 23 GC patients eligible for camrelizumab treatment were collected. Flow cytometry was carried out to analyze the proportion of P2RX1 in neutrophils. IHC was utilized to detect the expression level of PD-L1. We also evaluated the chemotaxis ability of neutrophils using a Transwell system, assessed the viability and apoptosis rate of GC cells using CCK-8 and flow cytometry, measured the proportions of CD8+PD-1+ and CD8+GZMB+ cells, determined the expression levels of IL-6, TNFα, IFN-γ, IL-8, IL-12, IL-1β, and GZMB by utilizing enzyme-linked immunosorbent assay (ELISA), and examined the expression levels of P2RX1 and PD-L1 using western blot (WB). By establishing a xenograft mouse model, we studied the impact of P2RX1-blocked neutrophils on the efficacy of ICI treatment in the GC microenvironment.

In GC, clinical analysis revealed increased infiltration of P2RX1-lowly expressed neutrophil subsets and increased expression of PD-L1. In vitro experiments demonstrated that abnormal expression of P2RX1 affected neutrophil function. Furthermore, the blockage or knockdown of P2RX1 in neutrophils modulated CD8+ T cell function, promoting GC progression. In in vivo experiments, the blockage of P2RX1 in neutrophils inhibited the effectiveness of ICI treatment in the GC microenvironment.

This project validated that the loss of P2RX1 in neutrophils induces CD8+ T cell dysfunction and affects the GC development, indicating that P2RX1 may be an accurate biomarker for predicting ICI response, thus providing a theoretical basis for the clinical application of ICI.

The relationship between patient nutritional, immune, and inflammatory status is linked to tumor progression and prognosis. However, there are limited studies on the prognosis of esophageal squamous cell carcinoma (ESCC) after surgery based on the comprehensive indicators of these factors.

To develop and validate a novel nomogram based on a nutritional immune-inflammatory status (NIIS) score for predicting postoperative outcomes in ESCC.

This retrospective study examined 829 patients with ESCC who underwent radical surgery between June 2016 and June 2020, with 568 patients in the training cohort and 261 patients in the validation cohort. We incorporated comprehensive indicators related to nutrition, immunity, and inflammation to develop the NIIS score, using LASSO regression. Subsequently, a nomogram combining the NIIS score and other clinicopathological parameters was developed and validated using calibration curves, time-dependent area under curves, and decision curve analysis.

We identified eight indicators that constitute the NIIS score. High-risk scores emerged as an independent risk factor for overall survival [training set HR 2.497 (1.802, 3.458), P < 0.001]. A NIIS nomogram for personalized prognostic prediction was developed by integrating the NIIS score with clinicopathological variables, yielding enhanced predictive value relative to individual indicators and the UICC/TNM staging system.

The NIIS score provides strong predictive value for postoperative outcomes in ESCC, thus offering a valuable tool for clinical decision-making.

Digestive system carcinomas (DSC) constitute a significant proportion of solid tumors, with incidence rates rising steadily each year. The systemic inflammation response index (SIRI) has been identified as a potential prognostic marker for survival in various types DSC. This meta-analysis aimed to evaluate the prognostic value of SIRI in patients with DSC.

We conducted a comprehensive literature search of PubMed, Web of Science Core Collection, Embase, and Cochrane Library databases, searching for studies published from inception to May 30, 2023. Eligible studies included cohort studies that assessed the association between pre-treatment SIRI levels and DSC prognosis. We extracted and synthesized hazard ratios (HRs) and 95% confidence intervals (CIs) using STATA/SE 12.0, stratifying HRs based on univariable and multivariable analysis. Due to substantial heterogeneity, we applied a random-effect model for all pooled analyses. The primary outcome of interest was the overall survival (OS), while secondary outcomes included progression-free survival (PFS), disease-free survival (DFS), time to progression (TTP), and disease specific survival (DSS). Publication bias was evaluated using Begg's test and Egger's tests.

A total of 34 cohort studies encompassing 9628 participants were included in this meta-analysis. Notable heterogeneity was observedin the OS (I2 = 76.5%, p < 0.001) and PFS (I2 = 82.8%, p = 0.001) subgroups, whereas no significant heterogeneity was detected in the DFS, TTP, and DSS subgroups. Elevated SIRI was found to be significantly associated with shorter OS (HR = 1.98, 95% CI: 1.70-2.30, tau2 = 0.0966) and poorer PFS (HR = 2.36, 95% CI: 1.58-3.53, tau2 = 0.1319), DFS (HR = 1.80, 95% CI: 1.61-2.01, tau2 < 0.0001), TTP (HR = 2.03, 95% CI: 1.47-2.81, tau2 = 0.0232), and DSS (HR = 1.99, 95% CI: 1.46-2.72, tau2 < 0.0001). Furthermore, an increase in SIRI following treatment was linked to reduced OS, TTP, and DFS, while a decrease in SIRI post-treatment corresponded with improved OS, TTP, and DFS compared to baseline levels.

Elevated SIRI is associated with poorer clinical outcomes in patients with DSC. This index may serve as a valuable prognostic biomarker, offering a promising tool for predicting survival in DSC patients.

REGISTRATION NUMBER: CRD42023430962.

Breast cancer manifests as multiple subtypes with distinct patient outcomes and treatment strategies. Here, we optimized proteomic analysis of Formalin-Fixed Paraffin-Embedded (FFPE) specimens from patients diagnosed with five breast cancer subtypes, luminal A, luminal B, Her2, triple negative (TNBC) and metaplastic breast cancers (MBC), and from disease-free individuals undergoing reduction mammoplasty (RM). We identified and quantified ∼6,000 protein groups (with >2 peptides per protein) with significant changes in over 26% of proteins comparing each cancer subtype with control RM. Stringent statistical filters allowed us to deeply mine 576 significant conserved protein changes shared by all subtypes and protein changes unique to each subtype. The most aggressive subtype, MBC, revealed exacerbated stromal stress responses, as illustrated by a collagenolytic extracellular matrix (ECM) and immune participation biased towards neutrophils and eosinophils. Immunostaining of breast tissue sections confirmed differences across subtypes, in particular, a dramatic upregulation of SERPINH1, neutrophil-specific myeloperoxidase and eosinophil cationic protein in MBC. In summary, deep proteomic, digitalized protein abundance profiles, generated from FFPE breast cancer tissues, revealed significant changes in ECM and cellular proteins providing insight into clinically relevant states.

To evaluate the prognostic role of the preoperative pan-immune-inflammation value (PIV) index in patients with oral squamous cell carcinoma (OSCC) after undergoing radical resection and to develop a prognostic prediction model for these patients.

A large cohort study was conducted between January 2015 and March 2022. Univariate and multivariate Cox regression was used to assess the prognostic value of PIV, and propensity score matching (PSM) analysis was used to adjust for potential confounders. Randomized survival forest (RSF) was used to assess the relative importance of preoperative PIV in prognostic prediction. Finally, a Nomogram model was plotted to predict the prognosis of oral cancer patients.

A total of 779 patients were enrolled and followed up (mean follow-up time 34.14 ± 24.39). High PIV was significantly associated with worse survival in OSCC patients (hazard ratio [HR] = 1.62, 95% confidence interval [CI]: 1.15-2.29, P = 0.006). The same trend was observed in PSM (HR = 1.55,95% CI: 1.03-2.23, P = 0.035). RSF showed that PIV ranked third in the importance ranking of all prognostic factors. The calibration curves indicated that the Nomogram model was superior in predicting the prognostic 1-, 3-, and 5-year survival of oral cancer patients.

PIV is an independent predictor of prognosis in patients with oral squamous cell carcinoma, and a column-line graphical model based on PIV can effectively predict prognosis.

Preoperative peripheral hematological indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and prognostic nutritional index (PNI), exhibit promise as prognostic markers for glioma. This study evaluated the prognostic value of a combined scoring system incorporating NLR, PLR, MLR, and PNI, and developed a nomogram to predict glioma prognosis.

Data on preoperative NLR, PLR, MLR, and PNI were collected from 380 patients with pathologically diagnosed glioma (266 in the training cohort, 114 in the validation cohort). The Least Absolute Shrinkage and Selection Operator (Lasso) was employed to select relevant hematological indicators and generate a Lasso score. A nomogram was constructed utilizing Cox regression and Lasso variable selection. This nomogram incorporated the Lasso score, age, pathological type, chemotherapy status, and Ki67 expression to predict overall survival (OS). Model performance was evaluated utilizing Harrell's c-index, calibration curves, DCA, and clinical utility (stratification into low-risk and high-risk groups), and verified utilizing the independent validation cohort.

A total of 380 glioma patients were enrolled and separated into training (n = 266) and validation (n = 114) cohorts. The two cohorts demonstrated no significant differences in baseline characteristics. NLR, PLR, MLR, and PNI from the training dataset were utilized for Lasso calculation. Multivariable analysis indicated that age, pathological grade, chemotherapy status, Ki-67 expression, and the Lasso score were independent predictors of OS and were then included in the nomogram. The nomogram model based on the training cohort had a C index of 0.742 (95% CI: 0.700-0.783) and AUC values of 0.802, 0.775, and 0.815 for ROC curves at 1, 3, and 5 years after surgery. The validation cohort derived a similar C-index of 0.734 (95% CI: 0.671-0.798) and AUC values of 0.785, 0.778, and 0.767 at 1, 3, and 5 years, respectively. The nomogram demonstrated good calibration in both cohorts, indicating strong agreement between predicted and observed outcomes. The threshold probabilities for DCA at 1-, 3-, and 5-years post-surgery in the training and validation cohorts were 0.08~k0.74, 0.25~0.80, and 0.08~0.89, and 0.13~0.60, 0.28~0.81, and 0.25~0.88, respectively.

A nomogram incorporating a Lasso score effectively predicted prognosis in glioma patients. However, its performance did not significantly exceed that of standard clinical nomograms.

Tumor-associated neutrophils (TANs) play a critical role in the progression and prognosis of triple-negative breast cancer (TNBC), with N2-type TANs known for their pro-tumor characteristics. This study introduces CT-1, a derivative of cryptotanshinone that effectively suppresses TNBC growth while selectively reducing the proportion of N2-type TANs within tumor tissue. Notably, CT-1 induces simultaneous ferroptosis in both N2-type TANs and TNBC cells, a dual mechanism that enhances its therapeutic efficacy. The study identifies ferritin heavy chain 1 (FTH1), a key protein in iron metabolism, as the direct target of CT-1. By targeting FTH1, CT-1 facilitates the interaction between NCOA4 and ferritin, triggering ferritinophagy-mediated ferroptosis. These findings position CT-1 as a promising therapeutic agent, offering a strategy to combat TNBC by inducing ferroptosis in both N2-type TANs and cancer cells. This approach underscores the potential of FTH1 as a therapeutic target for treating TNBC.

There is emerging evidence that host related variables predict outcomes in various cancers. The Host index (H-index) incorporates various host-related, blood-derived biomarkers (immunological and nutritional parameters) as a single mathematical formula. The aim of this study was to evaluate outcomes using the H-index as a prognostic marker in gallbladder cancer (GBC) patients undergoing curative resection.

Retrospective cohort study of surgically treated GBCs at a tertiary cancer centre from January 2010 to May 2023 was performed. Patients who had received neoadjuvant therapy, metastatic (M1) disease at time of surgical exploration and incidental GBCs were excluded. Baseline neutrophil, lymphocyte, monocyte and platelet counts, hemoglobin and albumin levels were recorded. H-index was computed and analysed.

241 curatively resected GBC patients were included. The H-index was inversely associated with disease free survival (DFS), both on univariate (79.7 vs. 61.4% for H-index  3.4 respectively; p = 0.046) and multivariate analysis (Hazard ratio [HR] for recurrence: 1.954 [95% C.I.: 1.366-2.796]; p = < 0.001). Using the maximally distributed rank statistics, a cut-off of 1.31 showed a significant difference in 3-year DFS (86.2 vs. 68.4% for H-index  1.31 respectively; HR: 2.21 [95% CI: 1.16-4.21]; p = 0.013) but not overall survival (OS) (p = 0.269).

A higher H-index predicted for worse DFS in curatively resected GBC patients. This shows host related variables do play a role in influencing outcomes in GBC. However, larger prospective studies are required to further strengthen this finding.

Host-related, blood derived biomarkers can influence outcomes in various solid tumours. A higher baseline Host index (H-index) value which incorporates various blood-derived biomarkers, predicted for worse disease-free survival in curatively resected gallbladder cancers.

Recent research suggests that the emerging neutrophil-albumin ratio (NAR) has a significant correlation with the survival outcomes across a range of tumors, yet its predictive significance for nasopharyngeal carcinoma (NPC) remains insufficiently investigated. This study aimed to evaluate the relationship between the neutrophil-to-albumin ratio (NAR) and overall survival (OS) in patients with NPC, as well as to develop a corresponding prognostic model.

This retrospective analysis included 861 NPC patients treated with concurrent chemoradiotherapy (CCRT), who were randomly divided into a training group (n = 605) and a validation group (n = 256). To identify factors associated with OS and construct a prognostic nomogram, both univariate and multivariate Cox regression analyses were performed. The nomogram's prognostic accuracy was evaluated and independently validated.

The NAR score successfully segregated NPC patients into two categories with significantly different OS (HR = 0.536; 95 % CI: 0.296-0.972, P = 0.040). Through multivariate analysis, factors such as age, T stage, N stage, and NAR score were identified as independent predictors of OS, leading to the creation of a prognostic nomogram. This nomogram demonstrated superior predictive capability for OS [C-index = 0.702 (95 % CI: 0.636-0.768)], surpassing that of the conventional staging system [C-index = 0.651 (95 % CI: 0.549-0.752)]. The findings underwent internal validation within an independent cohort.

The NAR, an emergent biomarker combining nutritional and inflammatory status, offers a practical, low-cost, and non-invasive prognostic measure for NPC patients treated with CCRT. Additionally, the prognostic nomogram derived from NAR surpasses traditional staging systems in predictive accuracy.

Predicting the efficacy of immune-based therapy in patients with unresectable hepatocellular carcinoma (HCC) remains a clinical challenge. This study aims to evaluate the prognostic value of the systemic immune-inflammation index (SII) in forecasting treatment response and survival outcomes for HCC patients undergoing immune-based therapy.

We analyzed a cohort of 268 HCC patients treated with immune-based therapy from January 2019 to March 2023. A training cohort of 93 patients received atezolizumab plus bevacizumab (T + A), while a validation cohort of 175 patients underwent treatment with tyrosine kinase inhibitors (TKIs) combined with anti-PD-(L)1 therapy. The SII cutoff value, determined using X-tile analysis based on overall survival (OS) in the training cohort, divided patients into high (> 752*109) and low (≤ 752*109) SII groups. Prognostic factors were identified through univariate and multivariate logistic and Cox regression analyses, and survival outcomes were assessed using Kaplan-Meier methods. The predictive accuracy of SII was evaluated using receiver operating characteristic (ROC) curves.

An optimal SII cutoff of 752*109 stratified patients into high and low SII groups. Univariate and multivariate logistic regression indicated that SII was a significant predictor of the objective response rate (ORR), which was markedly different between the low and high SII subgroups (34.72% vs. 9.52%, P = 0.019). This finding was consistent in the validation cohort (34.09% vs. 16.28%, P = 0.026). SII also demonstrated prognostic value in Cox regression and Kaplan-Meier analyses. ROC curves confirmed that SII had superior predictive accuracy compared to common clinical indicators, with predictive relevance even in AFP-negative patients. Furthermore, a lower SII was associated with a higher T cell ratio and an increased number of CD8+ T cells and Granzyme B+ CD8+ T cells in peripheral blood.

SII is a promising predictor of both therapeutic efficacy and prognosis in HCC patients undergoing immune-based treatments. Its application may enhance clinical decision-making, thereby improving patient outcomes from immune-based therapy.

Pancreatic cancer (PC), known as the "king of cancers," is characterized by an exceptionally low five-year survival rate, posing a formidable challenge to global public health. N6-methyladenosine (m6A) methylation is prevalent across various stages of eukaryotic RNA expression, including splicing, maturation, stability, translation, and localization, and represents a pivotal mechanism of epigenetic regulation. m6A methylation influences tumor initiation and progression by modulating post-transcriptional processes, playing a critical role in sustaining cancer cell stemness, promoting cell proliferation, and mediating drug resistance. Extensive research underscores the substantial contribution of m6A modifications to PC development. However, the multiplicity of m6A regulators and their intricate mechanisms of action complicate the landscape. This review aims to deepen the understanding of m6A's role in PC by delineating its involvement in four key areas of tumorigenesis: the hypoxic tumor microenvironment, metabolic reprogramming, immune microenvironment, and resistance mechanisms. Additionally, the review addresses the emerging frontier of m6A interactions with non-coding RNAs (ncRNAs), offering insights into the potential therapeutic and prognostic applications of m6A in the treatment and prognosis prediction of PC.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and invasiveness and promote metastasis and cancer progression. By targeting various components of the TME, novel investigational strategies aim to disrupt the TME's contribution to the EMT, thereby improving treatment efficacy, addressing therapeutic resistance, and offering a nuanced approach to cancer therapy. This review scrutinizes the key players in the TME and the TME's contribution to the EMT, emphasizing avenues to therapeutically disrupt the interactions between the various TME components. Moreover, the article discusses the TME's implications for resistance mechanisms and highlights the current therapeutic strategies toward TME modulation along with potential caveats.

Aging is associated with a decline in immune function, termed immunosenescence, which compromises host defences and increases susceptibility to infections and cancer. Physical exercise is widely recognized for its myriad health benefits, including the potential to modulate the immune system. This review explores the bidirectional relationship between immunosenescence and physical exercise, focusing on their interplay in shaping antitumor immunity. We summarize the impact of aging on innate and adaptive immune cells, highlighting alterations that contribute to immunosenescence and cancer development. We further delineate the effects of exercise on immune cell function, demonstrating its potential to mitigate immunosenescence and enhance antitumor responses. We also discuss the implications of immunosenescence for the efficacy of immunotherapies, such as immune checkpoint inhibitors and adoptive T cell therapy, and explore the potential benefits of combining exercise with these interventions. Collectively, this review underscores the importance of understanding the complex relationship between immunosenescence, physical exercise, and antitumor immunity, paving the way for the development of innovative strategies to improve cancer outcomes in the aging population.

Neutrophils are key mediators of the immune response and play essential roles in the development of tumors and immune evasion. Emerging studies indicate that neutrophils also play a critical role in the immunotherapy resistance in cancer. In this review, firstly, we summarize the novel classification and phenotypes of neutrophils and describe the regulatory relationships between neutrophils and tumor metabolism, flora microecology, neuroendocrine and tumor therapy from a new perspective. Secondly, we review the mechanisms by which neutrophils affect drug resistance in tumor immunotherapy from the aspects of the immune microenvironment, tumor antigens, and epigenetics. Finally, we propose several promising strategies for overcoming tumor immunotherapy resistance by targeting neutrophils and provide new research ideas in this area.

Colorectal cancer (CRC) is often associated with metastasis and recurrence and is the leading cause of cancer-related mortality. In the progression of CRC, recent studies have highlighted the critical role of neutrophils, particularly tumor-associated neutrophils (TANs). TANs have both tumor-promoting and tumor-suppressing activities, contributing to metastasis, immunosuppression, angiogenesis, and epithelial-to-mesenchymal transition. Tumor-promoting TANs promote tumor growth by releasing proteases, reactive oxygen species, and cytokines, whereas tumor-suppressing TANs enhance immune responses by activating T cells and natural killer cells. Understanding the mechanisms underlying TAN mobilization, plasticity, and their role in the tumor microenvironment has revealed potential therapeutic targets. This review provides a comprehensive overview of TAN biology in CRC and discusses both the tumor-promoting and tumor-suppressing functions of neutrophils. Novel therapeutic approaches targeting TANs, such as chemokine receptor antagonists, aim to modulate neutrophil reprogramming and offer promising avenues for improving treatment outcomes of CRC.

Gastric cancer (GC) represents a prevalent malignancy globally, often diagnosed at advanced stages owing to subtle early symptoms, resulting in a poor prognosis. Exosomes are extracellular nano-sized vesicles and are secreted by various cells. Mounting evidence indicates that exosomes contain a wide range of molecules, such as DNA, RNA, lipids, and proteins, and play crucial roles in multiple cancers including GC. Recently, with the rapid development of mass spectrometry-based detection technology, researchers have paid increasing attention to exosomal cargo proteins. In this review, we discussed the origin of exosomes and the diagnostic and prognostic roles of exosomal proteins in GC. Moreover, we summarized the biological functions of exosomal proteins in GC processes, such as proliferation, metastasis, drug resistance, stemness, immune response, angiogenesis, and traditional Chinese medicine therapy. In summary, this review synthesizes current advancements in exosomal proteins associated with GC, offering insights that could pave the way for novel diagnostic and therapeutic strategies for GC in the foreseeable future.

Cancer and cardiovascular diseases are leading causes of death worldwide. Among them, breast cancer is one of the most common malignancies in women, while atrial fibrillation is one of the most extensively studied arrhythmias, with significant public health implications. As the global population ages and advancements in cancer treatments continue, the survival rates of breast cancer patients have significantly improved, leading to an increasing coexistence of breast cancer and atrial fibrillation. However, the mechanisms underlying this coexistence remain insufficiently studied, and there is no consensus on the optimal treatment strategies for these patients. This review consolidates existing research to systematically explore the epidemiological characteristics, risk factors, and pathophysiological mechanisms of both breast cancer and atrial fibrillation. It focuses on the unique signaling pathways associated with different molecular subtypes of breast cancer and their potential impact on the mechanisms of atrial fibrillation. Additionally, the relationship between atrial fibrillation treatment medications and breast cancer is discussed. These insights not only provide essential evidence for the precise prevention and management of atrial fibrillation in breast cancer patients but also lay a solid theoretical foundation for interdisciplinary clinical management practices.

Inhalation of respirable crystalline silica particles, including quartz, is associated with an increased risk of developing pathologies, including persistent lung inflammation, fibrosis, cancer, and systemic autoimmunity. We demonstrated that the nearly free silanols (NFS) generated upon quartz fracturing trigger the early molecular events determining quartz toxicity. Here, we address the involvement of NFS in driving short- and long-term pathogenic responses, including lung inflammation, fibrosis, cancer, and autoimmunity in multiple mouse models.

In vivo pulmonary responses to as-grown NFS-poor quartz (gQ) and fractured NFS-rich quartz (gQ-f) of synthetic origin were compared to two NFS-rich reference quartz dusts (Min-U-Sil 5, mQ-f). Acute and persistent inflammation, as well as fibrosis, were assessed 3 and 60 days, respectively, after administering one dose of particles (2 mg) via oropharyngeal aspiration (o.p.a.) to C57BL/6 mice. The carcinogenic potential was assessed in a co-carcinogenicity study using A/J mice, which were pre-treated with 3-methylcholanthrene (3-MC) and administered four doses of quartz particles (4 × 1 mg, o.p.a.), then sacrificed after 10 months. Autoimmunity was evaluated in autoimmune-prone 129/Sv mice 4 months after particle administration (2 × 1.25 mg, o.p.a). Mice exposed to NFS-rich quartz exhibited a strong acute lung inflammatory response, characterized by pro-inflammatory cytokine release and leukocyte accumulation, which persisted for up to 60 days. No inflammatory effect was observed in mice treated with NFS-poor gQ. Fibrosis onset (i.e., increased levels of pro-fibrotic factors, hydroxyproline, and collagen) was prominent in mice exposed to NFS-rich but not to NFS-poor quartz. Additionally, lung cancer development (tumour numbers) and autoimmune responses (elevated IgG and anti-dsDNA autoantibody levels) were only observed after exposure to NFS-rich quartz.

Collectively, the results indicate that NFS, which occur upon fracturing of quartz particles, play a crucial role in the short- and long-term local and systemic responses to quartz. The assessment of NFS on amorphous or crystalline silica particles may help create a predictive model of silica pathogenicity.

Bladder cancer was recognized as one of the most common malignant tumors in the urinary system, and treatment options remained largely limited to conventional surgery, radiotherapy, and chemotherapy, which limited patient benefits.

Researchers constructed an RNA transcriptome map of bladder cancer by integrating single-cell RNA sequencing and clinical data, identifying potential molecular targets for diagnosis and treatment. We also verified the antitumor activity of the target through in vitro experiment.

A distinct tumor cell subpopulation characterized by elevated S100A8 expression exhibited high copy number variation, high stemness, and low differentiation. It interacted with myeloid cells via the MIF-(CD74+CD44) and MIF-(CD74+CXCR4) signaling pathways. This study underscored KDELR2's role in promoting cell proliferation, invasion, and migration, providing new therapeutic insights. Prognostic analysis revealed that KDELR2 correlated with poor survival, higher immune scores, and increased macrophage infiltration.

The findings suggested that patients with high KDELR2 expression might benefit from immune checkpoint therapy. KDELR2 was also shown to enhance bladder cancer cell proliferation, invasion, and migration, highlighting it as a promising target for macrophage-focused drug development.

Exosomes can regulate the malignant progression of tumors by carrying a variety of genetic information and transmitting it to target cells. Recent studies indicate that exosomal circular RNAs (circRNAs) regulate multiple biological processes in carcinogenesis, such as tumor growth, metastasis, epithelial-mesenchymal transition, drug resistance, autophagy, metabolism, angiogenesis, and immune escape. In the tumor microenvironment (TME), exosomal circRNAs can be transferred among tumor cells, endothelial cells, cancer-associated fibroblasts, immune cells, and microbiota, affecting tumor initiation and progression. Due to the high stability and widespread presence of exosomal circRNAs, they hold promise as biomarkers for tumor diagnosis and prognosis prediction in blood and urine. In addition, designing nanoparticles targeting exosomal circRNAs and utilizing exosomal circRNAs derived from immune cells or stem cells provide new strategies for cancer therapy. In this review, we examined the crucial role of exosomal circRNAs in regulating tumor-related signaling pathways and summarized the transmission of exosomal circRNAs between various types of cells and their impact on the TME. Finally, our review highlights the potential of exosomal circRNAs as diagnostic and prognostic prediction biomarkers, as well as suggesting new strategies for clinical therapy.

Tumor-associated neutrophils (TANs) play a crucial role in tumor progression and exhibit prolonged survival. However, the mechanism underlying their extended lifespan and significance in laryngeal squamous cell carcinoma (LSCC) remains unclear. Herein, it is observed that apoptosis of TANs is significantly delayed owing to induction by tumor-derived G-CSF and GM-CSF through the activation of the PI3K-AKT signaling pathway, upregulation of anti-apoptotic Mcl-1 expression, and downregulation of activated Caspase-3 levels. It is found that prolonged survival of TANs leads to the accumulation of aged CXCR4+ neutrophils that exhibit potent immunosuppressive properties and are associated with poor patient prognosis. Furthermore, extended survival promotes the enhanced immunosuppressive function of CD8+ T cells by TANs, thereby facilitating the in vitro and in vivo progression and growth of human LSCC tumors. Importantly, this effect could be reversed by blocking G-CSF and GM-CSF stimulation of neutrophils. These findings elucidate the pivotal role of pathologically prolonged neutrophil survival in impairing CD8+ T cell immunity and suggest targeting it as a potential therapeutic strategy for tumors.