The integration of fecal microbiota transplantation (FMT) with immune checkpoint inhibitors (ICIs) presents a promising approach for enhancing cancer treatment efficacy and overcoming therapeutic resistance. This review critically examines the controversial effects of FMT on ICIs outcomes and elucidates the underlying mechanisms. We investigate how FMT modulates gut microbiota composition, microbial metabolite profiles, and the tumor microenvironment, thereby influencing ICIs effectiveness. Key factors influencing FMT efficacy, including donor selection criteria, recipient characteristics, and administration protocols, are comprehensively discussed. The review delineates strategies for optimizing FMT formulations and systematically monitoring post-transplant microbiome dynamics. Through a comprehensive synthesis of evidence from clinical trials and preclinical studies, we elucidate the potential benefits and challenges of combining FMT with ICIs across diverse cancer types. While some studies report improved outcomes, others indicate no benefit or potential adverse effects, emphasizing the complexity of host-microbiome interactions in cancer immunotherapy. We outline critical research directions, encompassing the need for large-scale, multi-center randomized controlled trials, in-depth microbial ecology studies, and the integration of multi-omics approaches with artificial intelligence. Regulatory and ethical challenges are critically addressed, underscoring the imperative for standardized protocols and rigorous long-term safety assessments. This comprehensive review seeks to guide future research endeavors and clinical applications of FMT-ICIs combination therapy, with the potential to improve cancer patient outcomes while ensuring both safety and efficacy. As this rapidly evolving field advances, maintaining a judicious balance between openness to innovation and cautious scrutiny is crucial for realizing the full potential of microbiome modulation in cancer immunotherapy.

Bladder cancer (BCa) remains a significant source of morbidity and mortality. BCa is one of the most expensive tumors to treat, in part because of a lack of nonsurgical options. The recent advent of immunotherapy, alone or in combination with other compounds, has improved therapeutic options. Resistance to immunotherapy remains common, and many patients do not have durable response. Recent advances indicate immunotherapy efficacy may be tied in part to the endogenous bacteria present in our body, more commonly referred to as the microbiome. Laboratory and clinical data now support the idea that a healthy microbiome is critical to effective response to immunotherapy. At the same time, pathogenic interactions between the microbiome and immune cells can also serve to drive formation of tumors, increasing the complexity of these interactions. Given the rising importance of immunotherapy in BCa, understanding how we might be able to alter the microbiome to improve therapeutic efficacy offers a novel route to improved patient care. The goal of this review is to examine our current understanding of microbial interactions with the immune system and cancer with an emphasis on BCa. We will further attempt to define both current gaps in knowledge and future directions that may yield beneficial results to the field.

The microbiome is essential for maintaining human health and is also a key factor in the development and progression of various diseases, including cancer. Growing evidence has highlighted the microbiome's significant impact on cancer development, progression, and treatment outcomes. As research continues to unfold, the microbiome and its modulation stand out as a promising frontier in cancer research and therapy. This review highlights current literature on the interplay between various cancer treatment modalities and human microbiotas, focusing on how the microbiome may affect treatment efficacy and toxicity and its potential as a therapeutic target to enhance future outcomes.

Colorectal cancer (CRC) is one of the most prevalent and lethal cancers worldwide, ranking third in incidence and second in mortality. While immunotherapy has shown promise in patients with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), its effectiveness in proficient mismatch repair (pMMR) or microsatellite stable (MSS) CRC remains limited. Recent advances highlight the gut microbiota as a potential modulator of anti-tumor immunity. The gut microbiome can significantly influence the efficacy of immune checkpoint inhibitors (ICIs), especially in pMMR/MSS CRC, by modulating immune responses and systemic inflammation. This review explores the role of the gut microbiota in pMMR/MSS CRC, the mechanisms by which it may enhance immunotherapy, and current strategies for microbiota modulation. We discuss the potential benefits of combining microbiota-targeting interventions with immunotherapy to improve treatment outcomes for pMMR/MSS CRC patients.

Bifidobacterium adolescentis is a key probiotic that has been proven to possess various bioactivities. A water-soluble heteropolysaccharide (BEP-1A) was isolated from the probiotic and systematically investigated for the first time. The molecular weight of BEP-1A was calculated to be 9.69 × 106 Da. Combined with monosaccharide composition, Fourier transform infrared (FT-IR) spectroscopy, methylation and nuclear magnetic resonance (NMR) analysis, BEP-1A was composed of mannose, glucose and galactose at a molar ratio of 0.11⁚4.30⁚1.32. The backbone included β-1,2-Glcp, β-1,3-Glcp, α-1,4-Glcp, α-1,4-Galp, α-1,6-Galp and α-1,3-Manp, with the branch at the O-2 position of α-1,6-Galp, consisting of α-1,2-Galp and α-1-Glcp. Moreover, a filamentous structure of BEP-1A was detected by scanning electron microscopy (SEM). BEP-1A presented high thermal stability based on thermogravimetric analysis (TGA). X-ray diffractometry (XRD) results revealed that BEP-1A was an amorphous molecule without a crystal structure. Furthermore, BEP-1A significantly increased the viability of RAW 264.7 macrophages, improved phagocytosis, and promoted the secretion of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS). BEP-1A was also found to induce the nuclear translocation of the NF-κB subunit p65 and upregulate the phosphorylation of p65 and IκB-α, which suggested that the NF-κB pathway was involved in the BEP-1A-induced immunomodulatory effect. Overall, this study provides a theoretical basis for the development of BEP-1A as an immunomodulator in pharmaceuticals and functional foods.

The gut microbiome is interlinked with renal cell carcinoma (RCC) and its response to systemic treatment. Mounting data suggests that certain elements of the gut microbiome may correlate with improved outcomes. New generation sequencing techniques and advanced bioinformatic data curation are accelerating the investigation of specific markers and metabolites that could predict treatment response. A variety of new therapeutic strategies, such as fecal microbiota transplantation, probiotic supplements, and dietary interventions, are currently being developed to modify the gut microbiome and improve anticancer therapies in patients with RCC. This review discusses the preliminary evidence indicating the role of the microbiome in cancer treatment, the techniques and tools necessary for its proper study and some of the current forms with which the microbiome can be modulated to improve patient outcomes.

This review delves into the complex and multi-layered mechanisms that govern the interaction between gut microbiota and T cells in the context of colorectal cancer (CRC), revealing a novel "microbiota-immune regulatory landscape" within the tumor microenvironment. As CRC progresses, the gut microbiota experiences a significant transformation in both its composition and metabolic patterns. On one hand, specific microbial entities within the gut microbiota can directly engage with T cells, functioning as "immunological triggers" that shape T-cell behavior. Simultaneously, microbial metabolites, such as short-chain fatty acids and bile acids, serve as "molecular regulators" that intricately govern T-cell function and differentiation, fine-tuning the immune response. On the other hand, the quorum-sensing mechanism, a recently recognized communication network among bacteria, also plays a pivotal role in orchestrating T-cell immunity. Additionally, the gut microbiota forms an intriguing connection with the neuro-immune regulatory axis, a largely unexplored "territory" in CRC research. Regarding treatment strategies, a diverse array of intervention approaches-including dietary modifications, the utilization of probiotics, bacteriophages, and targeted antibiotic therapies-offer promising prospects for restoring the equilibrium of the gut microbiota, thereby acting as "ecosystem renovators" that impede tumor initiation and progression. Nevertheless, the current research landscape in this field is fraught with challenges. These include significant variations in microbial composition, dietary preferences, and tumor microenvironments among individuals, a lack of large-scale cohort studies, and insufficient research that integrates tumor mutation analysis, gut microbiota investigations, and immune microenvironment evaluations. This review emphasizes the necessity for future research efforts to seamlessly incorporate multiple factors and utilize bioinformatics analysis to construct a more comprehensive "interactive map" of the gut microbiota-T cell relationship in CRC. The aim is to establish a solid theoretical basis for the development of highly effective and personalized treatment regimens, ultimately transforming the therapeutic approach to CRC.

Lung cancer remains one of the most widespread and deadliest malignant tumors globally, with a particularly high mortality rate among all cancers. Recently, immunotherapy, particularly immune checkpoint inhibitors (ICIs), has emerged as a crucial treatment strategy for lung cancer patients, following surgical intervention, radiotherapy, chemotherapy, and targeted drug therapies. However, the therapeutic limitations are caused owing to their low response rate and undesirable side effects such as immune-related pneumonitis. Therefore, developing new strategies to improve the efficacy of ICIs while minimizing immune-related adverse events will be crucial for cancer immunotherapy. The tumor immune microenvironment plays a significant role in the success of lung cancer immunotherapy, and the immunosuppressive characteristics of the immune microenvironment are one of the major obstacles to the poor immunotherapeutic effect. Phytochemicals, naturally occurring compounds in plants, have shown promise in enhancing cancer immunotherapy by remodeling the immunosuppressive microenvironment, offering the potential to increase the efficacy of ICIs. Therefore, this review summarizes the associated mechanisms of phytochemicals remodeling the immunosuppressive microenvironment in lung cancer. Additionally, the review will focus on the synergistic effects of combining phytochemicals with ICIs, aiming to improve anticancer efficacy and reduce side effects, which may hopefully offer novel strategies to overcome current limitations in immunotherapy.

The gut microbiota exhibits intricate connections with the body's immune system and holds significant implications for various diseases and cancers. Currently, accumulating evidence suggests a correlation between the composition of the gut microbiota and the development, treatment, and prognosis of melanoma. However, the underlying pathogenesis remains incompletely elucidated. In this comprehensive review, we present an in-depth review of the role played by gut microbiota in melanoma tumorigenesis, growth, metastasis, treatment response, and prognosis. Furthermore, we discuss the potential utility of gut microbiota as a promising prognostic marker. Lastly, we summarize three routes through which gut microbiota influences melanoma: immunity, aging, and the endocrine system. By modulating innate and adaptive immunity in patients with melanoma across different age groups and genders, the gut microbiota plays a crucial role in anti-tumor immune regulation from tumorigenesis to prognosis management, thereby impacting tumor growth and metastasis. This review also addresses current study limitations while highlighting future research prospects.

Although immune checkpoint inhibitors (ICIs) are widely used in clinical oncology, less than half of treated cancer patients derive benefit from this therapy. Both tumor- and host-related variables are implicated in response to ICIs. The predictive value of PD-L1 expression is confined only to several cancer types, so this molecule is not an agnostic biomarker. Highly elevated tumor mutation burden (TMB) caused either by excessive carcinogenic exposure or by a deficiency in DNA repair is a reliable indicator for ICI efficacy, as exemplified by tumors with high-level microsatellite instability (MSI-H). Other potentially relevant tumor-related characteristics include gene expression signatures, pattern of tumor infiltration by immune cells, and, perhaps, some immune-response modifying somatic mutations. Host-related factors have not yet been comprehensively considered in relevant clinical trials. Microbiome composition, markers of systemic inflammation [e.g., neutrophil-to-lymphocyte ratio (NLR)], and human leucocyte antigen (HLA) diversity may influence the efficacy of ICIs. Studies on ICI biomarkers are likely to reveal modifiable tumor or host characteristics, which can be utilized to direct the antitumor immune defense. Examples of the latter approach include tumor priming to immune therapy by cytotoxic drugs and elevation of ICI efficacy by microbiome modification.

Pancreatic cancer ranks among the most lethal digestive malignancies, exhibiting a steadily increasing incidence and mortality worldwide. Despite significant advances in cancer research, the 5-year survival rate remains below 10%, predominantly due to delayed diagnosis and limited therapeutic options. Concurrently, the gut microbiota-an integral component of host physiology-has emerged as a crucial player in the pathogenesis of pancreatic cancer. Mounting evidence indicates that alterations in gut microbial composition and function may influence tumor initiation, progression, and response to therapy. This review provides an in-depth examination of the intricate interplay between the gut microbiome and pancreatic cancer, highlighting potential diagnostic biomarkers and exploring microbiome-targeted therapeutic strategies to improve patient outcomes.

The evidence suggests that the microbiome plays a crucial role in cancer development. The oral cavity has many microorganisms that can influence oral cancer progression. Understanding the mechanisms and signaling pathways of the oral, gum, and teeth microbiome in tumor progression can lead to new treatment strategies. Probiotics, which are friendly microorganisms, have shown potential as anti-cancer agents. These positive characteristics of probiotic strains make them suitable for cancer prevention or treatment. The oral-gut microbiome axis supports health and homeostasis, and imbalances in the oral microbiome can disrupt immune signaling pathways, epithelial barriers, cell cycles, apoptosis, genomic stability, angiogenesis, and metabolic processes. Changes in the oral microbiome in oral cancer may suggest using probiotics-based treatments for their direct or indirect positive roles in cancer development, progression, and metastasis, specifically oral squamous cell carcinoma (OSCC). Here, reported relationships between probiotics, oral microbiota, and oral cancer are summarized.

Microbial impact on tumorigenesis of heritable cancers proximal to the gut is well-documented. Whether the microbiota influences cancers arising from inborn mutations at sites distal to the gut is undetermined. Using two models of heritable cancer, Trp53-deficient mice and Wnt1-transgenic mice, and a gnotobiotic approach, we found the microbiota to be inconsequential for tumor development. This work furthers our understanding of the degree of the microbial impact on tumor development.

The influence of the microbiome on the development of cancer is well-documented with many if not all published studies reporting either a positive or a negative impact. None of the published studies, however, presented data on the influence of the microbiome on the development of heritable cancer. We find that the microbiota has no influence on cancer development in two models of spontaneous cancers driven by germline Trp53 deficiency and constitutive Wnt1 signaling.

In the last decade, it has been discovered that intestinal flora can affect various organ-specific cancers by altering the body's energy balance, synthesizing genetic toxins and small signaling molecules, and initiating and modulating immune responses. In this review, we will focus on elucidating the role of intestinal flora based on its molecular mechanisms and its possible impact on head and neck cancers in the near future, and explore how it may be a novel approach to treating head and neck cancers in the future.

In order to decipher the relationship between gut microbiota imbalance and cancer, this paper reviewed the role of intestinal microbiota in anticancer therapy and related mechanisms, discussed the current research status of gut microbiota as a biomarker of cancer, and finally summarized the reasonable means of regulating gut microbiota to assist cancer therapy. Overall, our study reveals that the gut microbiota can serve as a potential target for improving cancer management.

To investigate the gut microbiome of lung cancer patients with brain metastases undergoing radiotherapy, identify key microorganisms associated with radiotherapy response, and evaluate their potential as biomarkers.

This study enrolled 55 newly diagnosed lung cancer patients with brain metastases. Fecal samples were collected before radiotherapy and analyzed by 16S rRNA sequencing to assess the gut microbiome's composition and function. Patients were categorized into response (n=28) and non-response (n=27) groups based on treatment efficacy, and α-diversity, β-diversity, and functional pathways were compared between them. Linear Discriminant Analysis Effect Size was used to identify microbial features associated with treatment efficacy. Logistic regression analyses were performed to evaluate the predictive capacity of clinical and microbial factors for treatment outcomes.

No significant difference in α-diversity was observed between the groups (P > 0.05), but β-diversity differed significantly (P = 0.036). Twelve characteristic microorganisms were identified in the response group, including g_ Oscillibacter and g_ Blautia, and nine in the non-response group, such as f_ Desulfovibrionaceae and g_ Megamonas. Metabolic pathways associated with treatment response included ketone body metabolism and pathways related to amyotrophic lateral sclerosis. Multivariate analysis identified g_Flavonifractor (odds ratio [OR] = 6.680, P = 0.004), g_Negativibacillus (OR = 3.862, P = 0.014), C-reactive protein (OR = 1.054, P = 0.017), and systemic inflammation response index (OR = 1.367, P = 0.043) as independent predictors of radiotherapy response. The nomogram and microbiome models achieved area under the curve (AUC) values of 0.935 and 0.866, respectively, demonstrating excellent predictive performance. Decision curve analysis further confirmed these models provided significant net benefits across risk thresholds.

The composition and functional characteristics of the gut microbiome in lung cancer patients with brain metastases prior to radiotherapy are associated with therapeutic response and possess potential as predictive biomarkers. Further studies are warranted to validate these findings.

Anti-tumor immunity, including innate and adaptive immunity is critical in inhibiting tumorigenesis and development of tumor. The adaptive immunity needs specific lymph organs such as tertiary lymphoid structures (TLSs), which are highly correlated with improved survival outcomes in many cancers. In recent years, with increasing attention on the TLS in tumor microenvironment, TLSs have emerged as a novel target for anti-tumor therapy. Excitingly, studies have shown the contribution of TLSs to the adaptive immune responses. However, it is unclear how TLSs to form and how to more effectively defense against tumor through TLS formation. Recent studies have shown that the inflammation plays a critical role in TLS formation. Interestingly, studies have also found that gut microbiota can regulate the occurrence and development of inflammation. Therefore, we here summarize the potential effects of gut microbiota- mediated inflammation or immunosuppression on the TLS formation in tumor environments. Meanwhile, this review also explores how to manipulate mature TLS formation through regulating gut microbiota/metabolites or gut microbiota associated signal pathways for anti-tumor immunity, which potentially lead to a next-generation cancer immunotherapy.

Colorectal cancer (CRC) poses a significant global health burden, with gut microbiota emerging as a crucial modulator of CRC pathogenesis and therapeutic outcomes. This review synthesizes current evidence on the influence of gut microbiota on tumor immune surveillance and responses to immunotherapies and chemotherapy in CRC. We highlight the role of specific microbial taxa in promoting or inhibiting tumor growth and the potential of microbiota-based biomarkers for predicting treatment efficacy. The review also discusses the implications of microbiota modulation strategies, including diet, probiotics, and fecal microbiota transplantation, for personalized CRC management. By critically evaluating the literature, we aim to provide a comprehensive understanding of the gut microbiota's dual role in CRC and to inform future research directions in this field.

With nearly half of colorectal cancer (CRC) patients diagnosed at advanced stages where surgery alone is insufficient, chemotherapy remains a cornerstone for this cancer treatment. To prevent infections and improve outcomes, antibiotics are often co-administered. However, chemotherapeutic interactions with the gut microbiota cause significant non-selective toxicity, affecting not only tumor and normal epithelial cells but also the gut microbiota. This toxicity triggers the bacterial SOS response and loss of microbial diversity, leading to bacterial mutations and dysbiosis. Consequently, pathogenic overgrowth and systemic infections increase, necessitating broad-spectrum antibiotics intervention. This review underscores how prolonged antibiotic use during chemotherapy, combined with chemotherapy-induced bacterial mutations, creates selective pressures that drive de novo antimicrobial resistance (AMR), allowing resistant bacteria to dominate the gut. This compromises the treatment efficacy and elevates the mortality risk. Restoring gut microbial diversity may mitigate chemotherapy-induced toxicity and improve therapeutic outcomes, and emerging strategies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, show considerable promise. Given the global threat posed by antibiotic resistance to cancer treatment, prioritizing antimicrobial stewardship is essential for optimizing antibiotic use and preventing resistance in CRC patients undergoing chemotherapy. Future research should aim to minimize chemotherapy's impact on the gut microbiota and develop targeted interventions to restore microbial diversity affected during chemotherapy.

Immune checkpoint inhibitor (ICI) therapy has yielded revolutionary outcomes among some individuals with skin cancer, but a large percentage of individuals do not benefit from these treatments. The gut microbiota is hypothesized to impact ICI therapy outcomes. However, data on ICI therapy, gut microbiota, and non-melanoma skin cancers are limited. To examine the association of gut microbiota structure and function with non-melanoma skin cancer ICI outcomes, we performed 16S rRNA V1-V2 gene amplicon sequencing of 68 fecal samples collected longitudinally from individuals with basal cell carcinoma (n = 5), Merkel cell carcinoma (n = 5), or cutaneous squamous cell carcinoma (CSCC, n = 11), followed by tumor-dependent differential analyses of bacterial composition and fecal sample analysis by untargeted metabolomics. Across all tumor types, we identified 10 differential bacterial genera between responders (R) or non-responders (NR) to ICI therapy. Among individuals with CSCC, we identified 10 genera and 20 species that differentiated between R and NR and yielded 8 pathways enriched in NR and 12 pathways enriched in R by predicted functional pathway analyses. Untargeted fecal metabolomics to examine putative gut microbiota metabolites associated with CSCC ICI R/NR identified nine KEGG pathways associated with ICI efficacy. In summary, this exploratory study suggests gut microbiota features that are associated with ICI efficacy in individuals with non-melanoma skin cancers and highlights the need for larger studies to validate the results.IMPORTANCEPrior studies examining associations between ICI efficacy and the gut microbiome have focused primarily on individuals with melanoma, for whom ICI therapy was first approved. Meanwhile, data regarding microbiome features associated with ICI responses in individuals with non-melanoma skin cancers (NMSCs) have remained limited. This initial fecal microbiota examination of individuals with NMSCs suggests that larger-scale studies to extend and validate our findings may yield predictive or prognostic biomarkers for individuals with NMSC receiving ICI with potential to provide insight to complementary, effective therapeutic interventions through microbiota modification.

The standard first-line treatment for driver-gene negative advanced non-small cell lung cancer (NSCLC) is chemotherapy combined with immunotherapy. However, owing to the immune microenvironment imbalance and immune status impairment caused by repeated chemotherapy, as well as the primary or secondary resistance to immune checkpoint inhibitors, the efficacy of immunotherapy combined with chemotherapy remains unsatisfactory. Recent studies have shown that faecal microbiota transplantation (FMT) can modulate the intestinal microflora, influence the tumour immune microenvironment and even enhance the efficacy of immunotherapy. Hence, we conduct such a prospective, exploratory study to evaluate the efficacy and safety of integrating FMT with standard first-line treatment in patients with driver-gene negative advanced NSCLC.

FMT-JSNO-02 (NCT06403111) is a prospective, multicentre, single-arm exploratory study. It is planned to include 62 cases of previously untreated driver-gene negative, Eastern Cooperative Oncology Group Performance Status 0-1, programmed death ligand 1<50% advanced NSCLC patients, who will be given FMT by orally ingested stool capsules on the basis of standard first-line treatment of chemotherapy combined with immunotherapy. The primary endpoint of this study is the 12-month progression-free survival rate.

The study was approved by the ethics committee of the Second People's Hospital of Changzhou (number [2024] YLJSA005) and is being conducted in accordance with the principles of the Declaration of Helsinki. The results of this study will be disseminated through publication in a peer-reviewed journal and presentation at scientific conferences.

NCT06403111. Date of registration: 7 May 2024, the first version protocol.

The Bifidobacterium genus is a prominent bacterial population in the gastrointestinal tract. Previous findings suggest that Bifidobacterium is linked to tumor suppression in mouse models of melanoma. Additionally, when combined with the programmed death-ligand 1 (PD-L1) antibody, it can enhance anti-tumor treatment by increasing tumor-specific T-cell responses and promoting infiltration of antigen-specific T cells into tumors. However, there is a lack of studies on Bifidobacterium in esophageal squamous cell carcinoma (ESCC). This study aimed to investigate the potential impact of Bifidobacterium on this cancer type.

We examined 213 samples from ESCC patients who underwent tumor resection. The presence of Bifidobacterium was confirmed using quantitative polymerase chain reaction and fluorescent in situ hybridization (FISH). Patient overall survival (OS) was analyzed with Bifidobacterium positivity. Tumor-infiltrating lymphocytes (TILs) were evaluated via hematoxylin and eosin stains, and immunohistochemistry was used to assess programmed death-1 (PD-1), PD-L1, cluster of differentiation 8 (CD8), and forkhead box P3 (FOXP3) expression. Nutritional status was evaluated via computed tomography scans.

Bifidobacterium positivity showed no correlation with patient OS or TIL levels; however, Bifidobacterium positivity in normal tissue was associated with lower FOXP3 levels, suggesting a potential role in upregulating anti-tumor immune responses. Patients with Bifidobacterium present in peritumor normal tissue exhibited better skeletal muscle area and volume. Conversely, Bifidobacterium positivity in tumor tissue was associated with poorer prognostic nutrition index values, likely due to decreased albumin levels.

Bifidobacterium can induce the upregulated anti-tumor immune response and is more prevalent in cases with good nutritional status.

Immune checkpoint inhibitors (ICIs) have been approved for treatment of microsatellite instable (MSI-H) metastatic colorectal cancer (mCRC), but factors associated with receipt and efficacy of ICIs in routine clinical practice remain largely unknown.

To identify factors associated with receipt of ICIs and associated survival outcomes among patients with mCRC in routine clinical practice.

This population-based cohort study used deidentified data from a nationwide electronic health record-derived database to include 18 932 patients diagnosed with mCRC between January 2013 and June 2019. Population-based patients were diagnosed with de novo mCRC and had at least 2 documented clinical visits on or after the date of diagnosis. The study analyses were performed between September 2020 and April 2021.

Patients received ICI therapy and/or chemotherapy as part of a systemic treatment for mCRC.

The outcomes were receipt of ICI therapy, overall survival (OS), and time to treatment discontinuation (TTD).

In this cohort study of 18 932 patients diagnosed with mCRC (10 537 [55.7%] male; 546 [2.9%] Asian, 2005 [10.6%] Black or African American, 1674 [8.8%] Hispanic, 12 338 [65.2%] White, 4043 [21.4%] unknown race or ethnicity; median [IQR] age at metastatic diagnosis, 64.6 [55.0-73.3] years), patients with MSI-H tumors had a significantly higher probability of receiving ICIs than those with microsatellite stable (MSS) tumors (odds ratio [OR], 22.66 [95% CI, 17.30-29.73]; P < .001), whereas patients initially diagnosed with synchronous mCRC had significantly lower odds of receiving ICIs than patients with metachronous mCRC (OR, 0.57 [95% CI, 0.45-0.73]; P < .001). Patients with MSI-H tumors who received ICIs as first line of therapy had significantly longer OS than those receiving chemotherapy only (HR, 0.37 [95% CI, 0.25-0.56]; P < .001). Among patients with MSS tumors, ICI-based therapy was associated with significantly longer OS for patients with high albumin level (vs low: HR, 0.28 [95% CI, 0.18-0.45]; P < .001) and antibiotic use (vs nonuse: HR, 0.43 [95% CI, 0.27-0.67]; P < .001), but a significantly shorter OS for patients with synchronous mCRC (vs metachronous: HR, 1.90 [95% CI, 1.24-2.89]; P = .003). In addition, 29 out of 235 patients with MSS tumors (12.3%) experienced durable responses on ICI-based therapy. Similar patterns of associations with TTD were observed.

In this cohort study of patients with mCRC, clinical characteristics were associated with different survival outcomes in patients treated with ICI-based therapy, with important clinical implications for patients with MSS tumors who are generally unresponsive to immunotherapy.

Adolescence is a crucial period marked by profound changes in the brain. Exposure to psychological stressors such as bullying, abuse or maltreatment during this developmental period may increase the risk of developing depression, anxiety and comorbid cardiometabolic conditions. Chronic psychological stress is associated with behavioral changes and disruption of the hypothalamic-pituitary-adrenal axis, leading to corticosterone overproduction in rodents and changes in both the immune system and the gut microbiome. Here, we demonstrate the ability of Bifidobacterium longum CECT 30763 (B. longum) to ameliorate adolescent depressive and anxiety-like behaviors in a chronic social defeat (CSD) mouse model. The mechanisms underlying this beneficial effect are related to the ability of B. longum to attenuate the inflammation and immune cell changes induced by CSD after the initial stress exposure through the induction of T regulatory cells with enduring effects that may prevent and mitigate the adverse consequences of repeated stress exposure on mental and cardiometabolic health. B. longum administration also normalized dopamine release, metabolism and signaling at the end of the intervention, which may secondarily contribute to the reversal of behavioral changes. The anti-inflammatory effects of B. longum could also explain its cardioprotective effects, which were reflected in an amelioration of the oxidative stress-induced damage in the heart and improved lipid metabolism in the liver. Overall, our findings suggest that B. longum regulates the links between the immune and dopaminergic systems from the gut to the brain, potentially underpinning its beneficial psychobiotic and physiological effects in CSD.

Previous research has identified bile acids (BAs) as a valuable supplement for animal feed, especially in the poultry industry. However, there is limited research on the use of bile acids as a preventative measure against intestinal inflammation in broilers. This study aims to investigate the impact of dietary BAs on LPS-triggered intestinal inflammation in broilers. 180 Arbor Acres broilers were randomly divided into four group: (1) broilers receiving a standard diet (Con group); (2) broilers from the Con category subjected to LPS challenge (LPS group); (3) broilers on a diet supplemented with BAs compound and exposed to LPS (BA+LPS group); and (4) broilers on a diet enriched with lithocholic acid (LCA) and challenged with LPS (LCA + LPS group).The results showed that the LPS challenge caused a notable rise in liver mass, plasma AST concentrations, and levels of inflammatory cytokines (P < 0.05). BAs compounds or LCA improved intestinal morphological damage, inflammation response and bile acid metabolism (P < 0.05). Furthermore, analysis of 16S rRNA gene sequences revealed that supplementation with BAs compounds or LCA mitigated the reduction in bacterial diversity, while also increasing the abundance of operational taxonomic units (OTUs) associated with Bacteroides and Bifidobacterium. Additionally, the increased abundance of Candidatus_Arthromitus due to BAs compound or LCA supplementation showed a significant negative correlation with the concentrations of intestinal inflammatory cytokines (P < 0.05). These results suggest that the supplementation of BAs compound or LCA has the potential to alleviate intestinal inflammation and regulate gut microbiota in broilers subjected to LPS challenge.

Immunotherapy with checkpoint inhibitors has become the cornerstone of systemic treatment for non-oncogene addicted non-small-cell lung cancer. Despite its pivotal role, a significant proportion of patients-approximately 70-85%-either exhibit primary resistance to PD-1 blockade or develop acquired resistance following an initial benefit, even in combination with chemotherapy and/or anti-CTLA-4 agents. The phenomenon of primary and acquired resistance to immunotherapy represents a critical clinical challenge, largely based on our incomplete understanding of the mechanisms of action of immunotherapy, and the resulting lack of accurate predictive biomarkers. Here, we review the definitions and explore the proposed mechanisms of primary and acquired resistance, including those related to the tumor microenvironment, systemic factors, and intrinsic tumor characteristics. We also discuss translational data on adaptive changes within tumor cells and the immune infiltrate following exposure to checkpoint inhibitors. Lastly, we offer a comprehensive overview of current and emerging therapeutic strategies designed to prevent primary resistance and counteract acquired resistance.

Melanoma, a highly aggressive form of skin cancer, has seen significant advancements in treatment through the introduction of immunotherapy. However, the variability in patient responses underscores the need for reliable biomarkers to guide treatment decisions. This article reviews key biomarkers in melanoma immunotherapy, such as PD-L1 expression, tumor mutational burden (TMB), and gene expression profiles (GEPs). It also explores emerging biomarkers, including LAG-3 expression, immune cell phenotyping in tissue and blood, gut microbiota, and circulating tumor DNA (ctDNA). Notably, ctDNA may offer valuable insights into the efficacy of T cell-engaging bispecific molecules, such as tebentafusp. The review provides a comprehensive overview of the evolving landscape of melanoma biomarkers, their role in personalizing treatment, and future research directions, including neoadjuvant immune checkpoint inhibition.

Pancreatic cancer (PCA), a leading cause of cancer-related deaths, has limited non-invasive diagnostic methods. We aimed to identify oral and fecal microbiome biomarkers and construct diagnostic classifiers. Oral and fecal samples from 97 PCA patients and 90 healthy controls underwent 16S rRNA sequencing. Samples were randomly divided into training and validation cohorts in a 7:3 ratio. Random forest models were constructed using training cohort and validated internally and externally in Chinese, Japanese, and Spanish populations. Results revealed significant dysbiosis of the oral and fecal microbiota of PCA patients. Most of the differential taxa shared between oral and fecal samples showed similar changes. Relative abundances of Streptococcus in oral samples, and of Bifidobacterium, Klebsiella and Akkermansia in fecal samples, were enriched in PCA. The fecal Firmicutes to Bacteroidota ratio was higher in PCA patient samples. Oral and fecal microbiome classifiers based on the top 20 contributing genera were constructed, and internal validation showed that the area under the curve (AUC) values were 0.963 and 0.890, respectively. The fecal microbiome classifier performed well in the external Chinese population, with an AUC of 0.878, but poorly in the Japanese and Spanish populations. Furthermore, fecal microbiomes could predict metastasis status in PCA patients, with an AUC of 0.804. In conclusion, oral and fecal microbiota were dysbiotic in PCA patients. Fecal microbiome classifier provides a feasible, non-invasive, and cost-effective tool with high precision for PCA screening in China; oral microbiome classifier requires further validation in external populations sampled with the same simple and convenient methods.

Tryptophan (Trp), an essential amino acid, is solely acquired through dietary intake. It is vital for protein biosynthesis and acts as a precursor for numerous key bioactive compounds. The Kynurenine Pathway and the Indole Pathway are the main metabolic routes and are extensively involved in the occurrence and progression of diseases in the digestive, nervous, and urinary systems. In the Kynurenine Pathway, enzymes crucial to tryptophan metabolism, indoleamine-2,3-dioxygenase 1 (IDO1), IDO2, and Trp-2,3-dioxygenase (TDO), trigger tumor immune resistance within the tumor microenvironment and nearby lymph nodes by depleting Trp or by activating the Aromatic Hydrocarbon Receptor (AhR) through its metabolites. Furthermore, IDO1 can influence immune responses via non-enzymatic pathways. The Kynurenine Pathway exerts its effects on tumor growth through various mechanisms, including NAD+ regulation, angiogenesis promotion, tumor metastasis enhancement, and the inhibition of tumor ferroptosis. In the Indole Pathway, indole and its related metabolites are involved in gastrointestinal homeostasis, tumor immunity, and drug resistance. The gut microbiota related to indole metabolism plays a critical role in determining the effectiveness of tumor treatment strategies and can influence the efficacy of immunochemotherapy. It is worth noting that there are conflicting effects of the Kynurenine Pathway and the Indole Pathway on the same tumor phenotype. For example, different tryptophan metabolites affect the cell cycle differently, and indole metabolism has inconsistent protective effects on tumors in different regions. These differences may hold potential for enhancing therapeutic efficacy.

The intestinal microbiota has major influence on human physiology and modulates health and disease. Complex host-microbe interactions regulate various homeostatic processes, including metabolism and immune function, while disturbances in microbiota composition (dysbiosis) are associated with a plethora of human diseases and are believed to modulate disease initiation, progression and therapy response. The vast complexity of the human microbiota and its metabolic output represents a great challenge in unraveling the molecular basis of host-microbe interactions in specific physiological contexts. To increase our understanding of these interactions, functional microbiota research using animal models in a reductionistic setting are essential. In the dynamic landscape of gut microbiota research, the use of germ-free and gnotobiotic mouse technology, in which causal disease-driving mechanisms can be dissected, represents a pivotal investigative tool for functional microbiota research in health and disease, in which causal disease-driving mechanisms can be dissected. A better understanding of the health-modulating functions of the microbiota opens perspectives for improved therapies in many diseases. In this review, we discuss practical considerations for the design and execution of germ-free and gnotobiotic experiments, including considerations around germ-free rederivation and housing conditions, route and timing of microbial administration, and dosing protocols. This comprehensive overview aims to provide researchers with valuable insights for improved experimental design in the field of functional microbiota research.

Growing evidence reveals that the tumor microbiome-comprising distinct microbial communities within neoplastic tissues-exerts a profound influence on cancer initiation, progression, and therapeutic response. These microbes actively reshape the tumor microenvironment (TME) through metabolite secretion, the modulation of immune pathways, and direct interactions with host cells, thereby affecting tumor biology and therapeutic outcomes. Despite substantial heterogeneity among cancer types, recent insights underscore the tumor microbiome's potential as both a diagnostic/prognostic biomarker and a targetable component for innovative treatments. In this review, we synthesize emerging knowledge on the mechanistic roles of tumor-associated microbiota in shaping the TME, with a focus on how these discoveries can guide novel therapeutic strategies. We further explore interdisciplinary advances, including the convergence of microbiomics and nanotechnology, to enhance drug delivery, circumvent resistance, and foster TME remodeling. By highlighting these cutting-edge developments, our review underscores the transformative potential of integrating tumor microbiome research into precision oncology and advancing more personalized cancer therapies.

Antibiotic therapy (ABT)-induced dysbiosis may affect the efficacy of immune checkpoint inhibitors (ICI) therapy. We investigated the association between ABT and real-world overall survival (rwOS) and progression-free survival (rwPFS) in patients with metastatic urothelial carcinoma (mUC) receiving ICI or cisplatin-based chemotherapy (CIS).

Three thousand, one hundred seventy-nine patients were included from a nationwide electronic health record-derived de-identified database. Three-month landmark Kaplan-Meier methods and log-rank tests were used to estimate rwOS/PFS between treatment modalities based on ABT groups (stratified by exposure, timing, excretion mode, and administration route). Cox proportional models with time-varying coefficients were used to investigate the associations between ABT, treatment modality, and rwOS/PFS.

A total of 402 (27.1%) ICI and 655 (38.6%) CIS patients received ABT (p < 0.001). ICI receipt (OR 0.65, p < 0.001) and advanced age (OR 0.98, p < 0.001) were associated with lower ABT use. ICI exclusive findings included a negative correlation with rwOS in patients who received post-treatment initiated (ICI median: pre-13.2 vs post-7.9 vs none-13.3 months; p = 0.009), oral (median oral-9.6 vs none-13.3 months, p = 0.03), and renally cleared (median renal-9.9 vs none-13.3 months, p = 0.04) ABT. ABT's effect was negatively associated with rwOS in ICI patients within first 6 months (HR 1.36, 95% CI 1.107-1.74, p = 0.01) but not thereafter (p = 0.7).

This study identified a potential ICI-specific negative correlation between ABT and rwOS in patients with mUC, specifically those exposed to ABT pills and receipt before treatment initiation. These results emphasize the importance of antibiotic stewardship and continued investigation of the role of gut microbiome in mUC treatment efficacy.

Immune checkpoint inhibitors (ICI) have become the first-line therapy in patients with advanced cutaneous squamous cell carcinoma (cSCC). Antibiotics (ATB) have been reported to reduce ICI response in cancers, but this has not been evaluated in cSCC.

To evaluate ATB exposure at the onset of ICI in cSCC patients and to analyze its impact on outcome.

This single-center retrospective study included all patients who started anti-PD-1 for cSCC between March 2019 and July 2023. Exposure to ATB within 3 months prior and after the onset of ICI (ATB 3-3), including patients exposed within 1 month prior and after (ATB 1-1) were recorded. Response to ICI and survival were compared between patients with or without ATB exposure.

Among 104 patients included, 45 % were classified into ATB 3-3 subgroup, and 20 % to ATB 1-1. Disease control rate at 3 months were lower in both ATB 1-1 and ATB 3-3 subgroups, compared to their control group (p = 0.02 and 0.03, respectively). The overall survival and disease specific survival were lower in the ATB 1-1 subgroup, compared to control group (p = 0.04 and p = 0.01, respectively). Median progression free survival was 127 days in ATB 1-1 group, significantly lower than the control group (not reached), p = 0.005.

ATB intake was very frequent at ICI initiation in cSCC patients. In our cohort, ATB use within 1 month before or after ICI initiation significantly impacted survival, highlighting the need for caution when prescribing antibiotics in this population.

Tumors are inherently embedded in systemic physiology, which contributes metabolites, signaling molecules, and immune cells to the tumor microenvironment. As a result, any systemic change to host metabolism can impact tumor progression and response to therapy. In this review, we explore how factors that affect metabolic health, such as diet, obesity, and exercise, influence the interplay between cancer and immune cells that reside within tumors. We also examine how metabolic diseases influence cancer progression, metastasis, and treatment. Finally, we consider how metabolic interventions can be deployed to improve immunotherapy. The overall goal is to highlight how metabolic heterogeneity in the human population shapes the immune response to cancer.

In recent years, numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment (TIME). However, to date, no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric methods.

To describe the current global research status on the correlation between gut microbiota and the TIME, and to identify the most influential countries, research institutions, researchers, and research hotspots related to this topic.

We searched for all literature related to gut microbiota and TIME published from January 1, 2014, to May 28, 2024, in the Web of Science Core Collection database. We then conducted a bibliometric analysis and created visual maps of the published literature on countries, institutions, authors, keywords, references, etc., using CiteSpace (6.2R6), VOSviewer (1.6.20), and bibliometrics (based on R 4.3.2).

In total, 491 documents were included, with a rapid increase in the number of publications starting in 2019. The country with the highest number of publications was China, followed by the United States. Germany has the highest number of citations in literature. From a centrality perspective, the United States has the highest influence in this field. The institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang University. However, the institution with the most citations was the United States National Cancer Institute. Among authors, Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this field. The most cited author was Fan XZ. The results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology, Cancers, and Frontiers in Oncology. The three most frequently used keywords were gut microbiota, tumor microenvironment, and immunotherapy.

This study systematically elaborates on the research progress related to gut microbiota and TIME over the past decade. Research results indicate that the number of publications has rapidly increased since 2019, with research hotspots including "gut microbiota", "tumor microenvironment" and "immunotherapy". Exploring the effects of specific gut microbiota or derived metabolites on the behavior of immune cells in the TIME, regulating the secretion of immune molecules, and influencing immunotherapy are research hotspots and future research directions.

As one part of the innate immune response to external stimuli, chronic inflammation increases the risk of various cancers, and tumor-promoting inflammation is considered one of the enabling characteristics of cancer development. Recently, there has been growing evidence on the role of anti-inflammation therapy in cancer prevention and treatment. And researchers have already achieved several noteworthy outcomes. In the review, we explored the underlying mechanisms by which inflammation affects the occurrence and development of cancer. The pro- or anti-tumor effects of these inflammatory factors such as interleukin, interferon, chemokine, inflammasome, and extracellular matrix are discussed. Since FDA-approved anti-inflammation drugs like aspirin show obvious anti-tumor effects, these drugs have unique advantages due to their relatively fewer side effects with long-term use compared to chemotherapy drugs. The characteristics make them promising candidates for cancer chemoprevention. Overall, this review discusses the role of these inflammatory molecules in carcinogenesis of cancer and new inflammation molecules-directed therapeutic opportunities, ranging from cytokine inhibitors/agonists, inflammasome inhibitors, some inhibitors that have already been or are expected to be applied in clinical practice, as well as recent discoveries of the anti-tumor effect of non-steroidal anti-inflammatory drugs and steroidal anti-inflammatory drugs. The advantages and disadvantages of their application in cancer chemoprevention are also discussed.

As a significant cause of global mortality, the cancer has also economic impacts. In the era of cancer therapy, mitigating side effects and costs and overcoming drug resistance is crucial. Microbial species can grow inside the tumor microenvironment and inhibit cancer growth through direct killing of tumor cells and immunoregulatory effects. Although microbiota or their products have demonstrated anticancer effects, the possibility of acting as pathogens and exerting side effects in certain individuals is a risk. Hence, several genetically modified/engineered bacteria (GEB) have been developed to this aim with ability of diagnosing and selective targeting and destruction of cancers. Additionally, GEB are expected to be considerably more efficient, safer, more permeable, less costly, and less invasive theranostic approaches compared to wild types. Potential GEB strains such as Escherichia coli (Nissle 1917, and MG1655), Salmonella typhimurium YB1 SL7207 (aroA gene deletion), VNP20009 (∆msbB/∆purI) and ΔppGpp (PTet and PBAD), and Listeria monocytogenes Lmat-LLO have been developed to combat cancer cells. When used in tandem with conventional treatments, GEB substantially improve the efficacy of anticancer therapy outcomes. In addition, public acceptance, optimal timing (s), duration (s), dose (s), and strains identification, interactions with other strains and the host cells, efficacy, safety and quality, and potential risks and ethical dilemmas include major challenges.

Molecular mimicry between commensal bacterial antigens and tumor-associated antigens (TAAs) has shown potential in enhancing antitumor immune responses. This study leveraged this concept using commensal bacterial antigens, termed OncoMimics, to induce TAA-derived peptide (TAAp)-specific cross-reactive cytotoxic T cells and improve the efficacy of peptide-based immunotherapies.

The discovery of OncoMimics primarily relied on a bioinformatics approach to identify commensal bacteria-derived peptide sequences mimicking TAAps. Several OncoMimics peptide (OMP) candidates were selected in silico based on multiple key parameters to assess their potential to elicit and ameliorate immune responses against TAAs. Selected OMPs were synthesized and tested for their affinity and stability on the major histocompatibility complex (MHC) in vitro and for their capacity to elicit cross-reactive OMP-specific/TAAp-specific CD8+T cell responses in human leukocyte antigen (HLA)-A2-humanized mice, human peripheral blood mononuclear cells (PBMC) and patients with cancer.

Selected OMPs demonstrated superior HLA-A2 binding affinities and stabilities compared with homologous TAAps. Vaccination of HLA-A2-humanized mice with OMPs led to the expansion of OMP-specific CD8+T cells that recognize both OMPs and homologous TAAps, exhibiting cytotoxic capacities towards tumor antigens and resulting in tumor protection in a prophylactic setting. Using PBMCs from HLA-A2+healthy donors, we confirmed the ability of OMPs to elicit potent cross-reactive OMP-specific/TAAp-specific CD8+ T-cell responses. Interestingly, we observed a high prevalence of OMP-specific T cells across donors. Cytotoxicity assays revealed that OMP-stimulated human T cells specifically targeted and killed tumor cells loaded with OMPs or TAAps. Preliminary data from an ongoing clinical trial (NCT04116658) support these findings, indicating that OMPs elicit robust OMP-specific/TAAp-specific CD8+T cell responses in patients. Initial immunomonitoring data revealed sustained T-cell responses over time, with T cells maintaining a polyfunctional, cytotoxic and memory phenotype, which is critical for effective antitumor activity and long-term immune surveillance.

These findings suggest that leveraging naturally occurring commensal-derived antigens through OMPs could significantly remodel the tumor immune landscape, offering guidance for a promising strategy for cancer peptide-based immunotherapies.

Skin cancer, including melanoma and non-melanoma types, presents a significant and growing global health challenge due to its increasing incidence and mortality rates. While conventional treatments such as surgical excision, immunotherapy, and targeted therapies are well-established, microorganism-based approaches represent an innovative and promising alternative. These therapies employ live, genetically engineered, or commensal bacteria, viral vectors, or bacterial components to achieve various therapeutic mechanisms, including tumor targeting, immune system modulation, vascular disruption, competitive exclusion, drug delivery, and direct oncolysis. Despite their potential, these approaches require further investigation to address safety concerns, optimize treatment protocols, and gain a comprehensive understanding of their long-term outcomes.

Microalgae present a novel and multifaceted approach to cancer therapy by modulating the tumor-associated microbiome (TAM) and the tumor microenvironment (TME). Through their ability to restore gut microbiota balance, reduce inflammation, and enhance immune responses, microalgae contribute to improved cancer treatment outcomes. As photosynthetic microorganisms, microalgae exhibit inherent anti-tumor, antioxidant, and immune-regulating properties, making them valuable in photodynamic therapy and tumor imaging due to their capacity to generate reactive oxygen species. Additionally, microalgae serve as effective drug delivery vehicles, leveraging their biocompatibility and unique structural properties to target the TME more precisely. Microalgae-based microrobots further expand their therapeutic potential by autonomously navigating complex biological environments, offering a promising future for precision-targeted cancer treatments. We position microalgae as a multifunctional agent capable of modulating TAM, offering novel strategies to enhance TME and improve the efficacy of cancer therapies.