• Fecal Microbiota Transplantation
• cancer immunotherapy
• controversial effects
• immune checkpoint inhibitors
• microbiome modulation

• Humans
• Fecal Microbiota Transplantation
• Immune Checkpoint Inhibitors/therapeutic use
• Gastrointestinal Microbiome
• Neoplasms/therapy
• Neoplasms/microbiology
• Animals
• Immunotherapy/methods
• Tumor Microenvironment/drug effects
• Treatment Outcome
• Combined Modality Therapy

• Colorectal cancer
• Diagnosis
• Immune checkpoint inhibitors
• Immune system
• Immunotherapy
• Therapeutics

• Humans
• Colorectal Neoplasms/therapy
• Colorectal Neoplasms/immunology
• Immunotherapy/methods
• Immune Checkpoint Inhibitors/therapeutic use
• Cancer Vaccines/therapeutic use
• Tumor Microenvironment/immunology
• Combined Modality Therapy

• Colon cancer
• Microsatellite instability
• NGS
• Prognosis
• Tumor mutational burden

• Humans
• Colonic Neoplasms/genetics
• Colonic Neoplasms/pathology
• Colonic Neoplasms/drug therapy
• Male
• Female
• High-Throughput Nucleotide Sequencing
• Middle Aged
• Mutation/genetics
• Aged
• Neoplasm Metastasis
• Microsatellite Instability
• Prognosis
• Survival Analysis
• Adult
• Aged, 80 and over
• Multivariate Analysis
• Proportional Hazards Models
• Microsatellite Repeats/genetics
• Kaplan-Meier Estimate

• Ricerca Corrente L4 Ministero della Salute
• F/310034/01-03/X56 Ministero della Salute

• Alterations
• MRD
• Management
• NGS
• Resistance
• dPCR

• Humans
• Patched-1 Receptor/genetics
• Immune Checkpoint Inhibitors/therapeutic use
• Biomarkers, Tumor/genetics
• Mutation
• Female
• Gastrointestinal Neoplasms/genetics
• Gastrointestinal Neoplasms/drug therapy
• Gastrointestinal Neoplasms/pathology
• Male
• Middle Aged
• Aged
• Prognosis
• Adult

• B202304018803 Hunan Provincial Health Commission
• 2023JJ60436 Hunan Natural Science Fund-Joint Sector Fund
• 2022JGB041 Postgraduate Education and Teaching Reform Project of Central South University

• Colorectal cancer
• Immune checkpoint inhibitors
• Immunotherapy
• Personalized medicine
• Predictive biomarkers
• Tumor mutational burden

• Humans
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/therapy
• Colorectal Neoplasms/drug therapy
• Mutation
• Biomarkers, Tumor/genetics
• Immunotherapy/methods
• Microsatellite Instability
• Immune Checkpoint Inhibitors/therapeutic use

• case series
• muscle-invasive bladder cancer
• neoadjuvant therapy
• pathological response
• tislelizumab

• Metabolomics
• Microplastic
• Omics
• Pollution
• Toxicity
• Transcriptome
• Wharf roach (Ligia exotica)

• TCR
• TMB
• biomarkers
• exome sequencing
• immunotherapy

• APC mutation
• Immune cell infiltration
• Immunotherapy
• Tumor mutation burden
• colon cancer

• No.2020J011258 Science and Technology Program of Fujian Province
• No.2020S3F009 Science and Technology Program of Putian

• Antitumor immunotherapy
• Checkpoint inhibitor (CPI)
• Immune checkpoint blockade (ICB)
• Immune checkpoint inhibitors (ICIs)
• Immune checkpoint molecules
• Immune checkpoint therapy (ICT)
• Tumor microenvironment (TME)
• γδT cells

• colorectal cancer
• drug resistance
• immune checkpoint inhibitors
• mechanism
• treatment

• MYCBP2
• immune checkpoint inhibitors
• myc binding protein 2
• prognosis
• thyroid cancer

Cuproptosis is a newly discovered new mechanism of programmed cell death, and its unique pathway to regulate cell death is thought to have a unique role in understanding cancer progression and guiding cancer therapy. However, this regulation has not been studied in low grade glioma (LGG) at present. In this study, data on low grade glioma patients were downloaded from the TCGA database. We screened the genes related to cuproptosis from the published papers and confirmed the lncRNAs related to them. We applied univariate/multivariate, and LASSO regression algorithms, finally identified 11 lncRNAs for constructing prognosis prediction models, and constructed a risk scoring model. The reliability and validity test of the model indicated that the model could well distinguish the prognosis and survival of LGG patients. Furthermore, the analyses of immunotherapy, immune microenvironment, as well as functional enrichment were also performed. Finally, we verified the expression of these six prognostic key lncRNAs using real-time polymerase chain reaction (RT-PCR). In conclusion, this study is the first analysis based on cuproptosis-related lncRNAs in LGG and aims to open up new directions for LGG therapy.

As our understanding of the mechanisms of cancer treatment has increased, a growing number of studies demonstrate pathways through which DNA damage repair (DDR) affects the immune system. At the same time, the varied response of patients to immune checkpoint blockade (ICB) therapy has prompted the discovery of various predictive biomarkers and the study of combination therapy. Here, our investigation explores the interactions involved in combination therapy, accompanied by a review that summarizes currently identified and promising predictors of response to immune checkpoint inhibitors (ICIs) that are useful for classifying oncology patients. In addition, this work, which discusses immunogenicity and several components of the tumor immune microenvironment, serves to illustrate the mechanism by which higher response rates and improved efficacy of DDR inhibitors (DDRi) in combination with ICIs are achieved.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and are now the preferred treatment for several tumor types. Though ICIs have shown remarkable efficacy in several cancer histologies, in many cases providing long-term disease control, not all patients will derive clinical benefit from such approaches. Given the lack of a reliable predictive biomarker for therapeutic responses to ICIs, we conducted a retrospective analysis of publicly available genomic data from a large pan-cancer cohort of patients receiving ICI-based immunotherapy. Consistent with previous results, patients in the combined cohort deriving a long-term survival benefit from ICIs were more likely to have a higher tumor mutational burden (TMB). However, this was not uniform across tumor-types, failing to predict for long-term survivorship in most non-melanoma cancers. Interestingly, long-term survivors in most cancers had conserved patterns of mutations affecting several genes. In melanoma, this included mutations affecting TET1 or PTPRD. In patients with colorectal cancer, mutations affecting TET1, RNF43, NCOA3, LATS1, NOTCH3, or CREBBP were also associated with improved prognosis, as were mutations affecting PTPRD, EPHA7, NTRK3, or ZFHX3 in non-small cell lung cancer, RNF43, LATS1, or CREBBP mutations in bladder cancer, and VHL mutations in renal cell carcinoma patients. Thus, this study identified several genes that may have utility as predictive biomarkers for therapeutic responses in patients receiving ICIs. As many have no known relationship to immunotherapy or ICIs, these genes warrant continued exploration, particularly for cancers in which established biomarkers such as PD-L1 expression or TMB have little predictive value.

Immune checkpoint inhibitors (ICIs) have made important breakthrough in anti-tumor therapy, however, no single biomarker can accurately predict their efficacy. Studies have found that tumor microenvironment is a key factor for determining the response to ICI therapy. Cytokine receptor 3 (C-X-C Motif Chemokine Receptor 3, CXCR3) pathway has been reported to play an important role in the migration, activation, and response of immune cells. We analyzed survival data, genomics, and clinical data from patients with metastatic urothelial carcinoma (mUC) who received ICI treatment to explore the relationship between CXCR3 pathway activation and the effectiveness of ICIs. The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort and six other cohorts receiving ICI treatment were used for mechanism exploration and validation. In the ICI cohort, we performed univariate and multivariate COX analyses and discovered that patients in the CXCR3-high group were more sensitive to ICI treatment. A Kaplan–Meier analysis demonstrated that patients in the high CXCR3-high group had a better prognosis than those in the CXCR3-low group (P = 0.0001, Hazard Ratio = 0.56; 95% CI 0.42−0.75). CIBERSORT analysis found that mUC patients in the CXCR3-high group had higher levels of activated CD8+ T cells, M1 macrophages, and activated NK cells and less regulatory T cell (Treg) infiltration. Immunogenicity analysis showed the CXCR3-high group had higher tumor neoantigen burden (TNB). Our study suggests that CXCR3 pathway activation may be a novel predictive biomarker for the effectiveness of immunotherapy in mUC patients.

• CXCR3 pathway
• Immune checkpoint inhibitors
• Immune microenvironment
• Immunotherapy
• Urothelial cancer

• CAMOIP
• biomarkers
• immune checkpoint inhibitors
• multi-omics
• web tools

• Colorectal adenocarcinoma
• Integrin superfamily
• Prognosis
• Signature
• Survival analysis
• TCGA

• cancer
• immune escape
• immune-checkpoint molecules
• immunotherapy
• miRNA mimetics
• microRNAs
• tumour microenvironment

• CTNNB1
• biomarker
• hepatocellular carcinoma
• immune checkpoint inhibitors
• prognosis

• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/immunology
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/therapy
• Cohort Studies
• Humans
• Immunotherapy
• Liver Neoplasms/diagnosis
• Liver Neoplasms/immunology
• Liver Neoplasms/therapy
• Mutation
• Prognosis
• Proportional Hazards Models
• beta Catenin/genetics
• beta Catenin/immunology

For colorectal cancer patients, traditional biomarker deficient mismatch repair/microsatellite instability (dMMR/MSI) is an accurate predictor of immune checkpoint inhibitors (ICIs). Recent years, researchers considered tumor mutation burden (TMB) as another predictive biomarker which means the number of nonsynonymous mutations in cancer cells. Several studies have proven that TMB can evaluate the efficacy of ICI therapy in diverse types of cancer, especially in non-small cell lung cancer and melanoma. However, studies on the association between TMB and the response to ICI therapy in colorectal cancer alone are still lacking. In this study, we aim to verify the effect of TMB as a biomarker in predicting the efficacy of ICIs in colorectal cancer.

We searched the PubMed and Ovid MEDLINE databases up to May 1, 2021 and screened studies for eligibility. Thirteen studies published from 2015 to 2021 with 5062 patients were included finally. We extracted and calculated hazard ratios (HRs) and odds ratios (ORs) of overall survival (OS) and objective response rates (ORRs) and their 95% confidence intervals (95% CIs). Pooled HR and OR were evaluated to compare OS and ORR between TMB-high and TMB-low groups in colorectal cancer patients. Meanwhile, we assessed heterogeneity with the I² statistic and p-values and performed publication bias assessments, sensitivity analyses, and subgroup analyses to search the cause of heterogeneity.

The TMB-high patient group had a longer OS than the TMB-low patient group (HR = 0.68, 95% CI: 0.51, 0.92, p = 0.013) among colorectal cancer patients receiving ICIs. In addition, the TMB-high patient group was superior in terms of ORR (OR = 19.25, 95% CI: 10.06, 36.82, p < 0.001) compared to the TMB-low patient group.

In conclusion, this meta-analysis revealed that TMB can be used as a potential predictive biomarker of colorectal cancer patients receiving ICI therapy. Nevertheless, this finding is not stable enough. Therefore, many more randomized controlled trials are needed to prove that TMB is reliable enough to be used clinically to predict the efficacy of immunotherapy in colorectal cancer. And the most relevant biomarker remains to be determined when TMB high overlaps with other biomarkers like MSI and TILs.

• colorectal cancer
• immune checkpoint inhibitors
• objective response rate
• overall survival
• tumor mutation burden

• FABP family genes
• FABP6
• bioinformatics
• colorectal cancer
• prognosis

• MOST 110-2320-B-038-017-MY3 Ministry of Science and Technology, Taiwan

Translational research on immune checkpoint inhibitors (ICIs) has been underway. However, in the unselected population, only a few patients benefit from ICIs. Therefore, screening predictive markers of ICI efficacy has become the current focus of attention. We collected mutation and clinical data from an ICI-treated non-small cell lung cancer (NSCLC) cohort. Then, a univariate Cox regression model was used to analyze the relationship between tumor necrosis factor α signaling mutated (TNFα-MT) and the prognosis of immunotherapy for NSCLC. We retrospectively collected 36 NSCLC patients (local-cohort) from the Zhujiang Hospital of Southern Medical University and performed whole-exome sequencing (WES). The expression and mutation data of The Cancer Genome Atlas (TCGA)-NSCLC cohort were used to explore the association between TNFα-MT and the immune microenvironment. A local cohort was used to validate the association between TNFα-MT and immunogenicity. TNFα-MT was associated with significantly prolonged overall survival (OS) in NSCLC patients after receiving immunotherapy. Additionally, TNFα-MT is related to high immunogenicity (tumor mutational burden, neoantigen load, and DNA damage response signaling mutations) and enrichment of infiltrating immune cells. These results suggest that TNFα-MT may serve as a potential clinical biomarker for NSCLC patients receiving ICIs.

• ICIs
• NSCLC
• TNFα
• biomarker
• tumor microenvironment

Urothelial cancer (UC) is one of the common refractory tumors and chemotherapy is the primary treatment for it. The advent of immune checkpoint inhibitors (ICI) has facilitated the development of treatment strategies for UC patients. To screen out UC patients sensitive to ICI, researchers have proposed that PD-L1, tumor mutation burden and TCGA molecular subtypes can be used as predictors of ICI efficacy. However, the performance of these predictors needs further validation. We need to identify novel biomarkers to screen out UC patients sensitive to ICI. In our study, we collected the data of two clinical cohorts: the ICI cohort and the TCGA cohort. The result of the multivariate Cox regression analysis showed that glycogen metabolism score (GMS) (HR = 1.26, p = 0.017) was the negative predictor of prognosis for UC patients receiving ICI treatment. Low-GMS patients had a higher proportion of patients achieving complete response or partial response to ICI. After the comparison of gene mutation status between high-GMS and low-GMS patients, we identified six genes with significant differences in mutation frequencies, which may provide new directions for potential drug targets. Moreover, we analyzed the immune infiltration status and immune-related genes expression between high-GMS and low-GMS patients. A reduced proportion of tumor-associated fibroblasts and elevated proportion of CD8⁺ T cells can be observed in low-GMS patients while several immunosuppressive molecules were elevated in the high-GMS patients. Using the sequencing data of the GSE164042 dataset, we also found that myeloid-derived suppressor cell and neutrophil related signature scores were lower in α-glucosidase knockout bladder carcinoma cells when compared to the control group. In addition, angiogenesis, classic carcinogenic pathways, immunosuppressive cells related pathways and immunosuppressive cytokine secretion were mainly enriched in high-GMS patients and cell samples from the control group. Finally, we suspected that the combination treatment of ICI and histone deacetylase inhibitors may achieve better clinical responses in UC patients based on the analysis of drug sensitivity data. In conclusion, our study revealed the predictive value of GMS for ICI efficacy of UC patients, providing a novel perspective for the exploration of new drug targets and potential treatment strategies.

• drug sensitivity
• gene mutation
• glycogen metabolism
• immune microenvironment
• immunotherapy
• pathway activation
• prognosis
• urothelial cancer

Colorectal liver metastases (CLM) occur in 15%-30% of patients with colorectal cancer (CRC). Advancements in next generation sequencing (NGS) can provide more precise prognoses for cancer patients and help guide clinical treatment. However, the genetic variants that predict high sensitivity to neoadjuvant chemotherapy remain unclear, especially in patients with CLM. The aim of this study was to identify the relevant genetic variants in a single CLM patient and to summarize the current evidence on mutations and single nucleotide polymorphisms (SNPs) that objectively predict sensitivity to neoadjuvant chemotherapy.

A 76-year-old male patient, who was diagnosed as stage IV colon cancer with liver metastases, was found to have APC/TP53/KRAS mutations. He showed a good therapeutic response to 12 courses of oxaliplatin regimens combined with Bevacizumab. Genetic analysis of the patient identified 5 genes with 7 detected SNPs that may be related to a better response to chemotherapy drugs. In addition, a critical literature review was performed based on a standardized appraisal form after selecting the articles. Ultimately, 21 eligible studies were appraised to assess the association between gene mutations and good prognosis. Mutations in KRAS, TP53, SMAD4, and APC were identified as being associated with a poor response to chemotherapy drugs, whereas mutations of CREBBP and POLD1 were associated with longer overall survival.

NGS can identify precise predictors of response to neoadjuvant chemotherapy, leading to improved outcomes for CRC patients.

• Colorectal liver metastases
• Next generation sequencing
• Neoadjuvant chemotherapy
• Genetic variants
• Case report

• immune microenvironment
• immunity
• lung adenocarcinoma
• single-cell sequencing
• spatial heterogeneity

Immune checkpoint inhibitors (ICIs) have made breakthrough progress in the treatment of various malignant tumors. However, only some patients receiving ICIs obtain long-lasting clinical effects, and some patients still do not achieve remission. Improving the treatment benefits of this part of the population has become a concern of clinicians. IL-1 signaling plays an important role in the tumor microenvironment (TME). However, the relationship between the IL-1 signaling mutation status and the prognosis of colon adenocarcinoma (COAD) patients receiving ICIs has not been reported. We downloaded the data of a COAD cohort receiving ICIs, including prognostic data and mutation data. Additionally, we downloaded the data of a COAD cohort from The Cancer Genome Atlas (TCGA) database, including clinical data, expression data and mutation data. Gene set enrichment analysis (GSEA) was used to assess differences in the activity of some key physiological pathways between the IL-1 signaling mutated-type (IL-1-MT) and IL-1 signaling wild-type (IL-1-WT) groups. The CIBERSORT algorithm was used to evaluate the contents of immune cells in the TME of COAD patients. The multivariate Cox regression model results suggested that IL-1-MT can be used as an independent predictor of a better prognosis in COAD patients receiving ICIs (P = 0.03, HR = 0.269, 95% CI: 0.082-0.883). Additionally, IL-1-MT COAD patients had significantly longer overall survival (OS) (log-rank P = 0.015). CIBERSORT analysis showed that the IL-1-MT group had high infiltration levels of activated dendritic cells (DCs), M1 macrophages, neutrophils, activated natural killer (NK) cells, activated CD4+ memory T cells and CD8+ T cells. Similarly, the IL-1-MT group had significantly upregulated immunogenicity, including in terms of the tumor mutation burden (TMB), neoantigen load (NAL) and number of mutations in DNA damage repair (DDR) signaling. GSEA showed that the IL-1-MT group was highly enriched in the immune response and proinflammatory mediators. Additionally, the expression levels of immune-related genes, immune checkpoint molecules and immune-related signatures were significantly higher in the IL-1-MT group than in the IL-1-WT group. IL-1-MT may be an independent predictor of a good prognosis in COAD patients receiving ICIs, with significantly longer OS in IL-1-MT COAD patients. Additionally, IL-1-MT was associated with significantly increased immunogenicity, activated immune cell and inflammatory mediator levels and immune response-related scores.

• IL-1
• colon adenocarcinoma
• immune checkpoint inhibitors
• prognosis
• tumor microenvironment

• DNA damage repair
• Immune checkpoint inhibitors
• hepatocellular carcinoma
• immunotherapy
• tumor microenvironment

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/genetics
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/therapy
• Child
• Child, Preschool
• Cohort Studies
• DNA Damage/genetics
• DNA Repair/genetics
• Drug Resistance, Neoplasm/genetics
• Female
• Gene Expression
• Humans
• Immune Checkpoint Inhibitors/therapeutic use
• Immunotherapy/methods
• Infant
• Infant, Newborn
• Kaplan-Meier Estimate
• Liver Neoplasms/genetics
• Liver Neoplasms/mortality
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Prognosis
• Risk Factors
• Treatment Outcome
• Tumor Microenvironment/immunology
• Young Adult

• CRC
• GNG4
• TCGA
• prognosis
• tumor mutation burden

Immunotherapy has emerged as an effective therapeutic strategy for various cancers, including colorectal cancer (CRC), but only a subset of MSI-H patients can benefit from such therapy. Patched1 (PTCH1) is a frequently altered gene in CRCs and its mutations contribute to unregulated Hedgehog (Hh) signaling. In the study, we evaluated the association of PTCH1 mutations with CRC immunity based on our single-center cohort and multiple cancer genomic datasets. Among 21 enrolled patients, six (28.6%) harbored a PTCH1 mutation based on WES analyses. In CRC patients, the PTCH1 mutation subgroup experienced a higher durable clinical benefit rate than the PTCH1 wild-type subgroup (100% vs. 40%, P = 0.017). In addition, patients with the PTCH1 mutation experienced greater progression-free survival (PFS, P = 0.037; HR, 0.208) and overall survival (OS, P = 0.045; HR, 0.185). A validation cohort from the MSKCC also confirmed the correlation between PTCH1 mutation and better prognosis (P = 0.022; HR, 0.290). Mechanically, diverse antitumor immune signatures were more highly enriched in PTCH1-mutated tumors than in PTCH1 wild-type tumors. Furthermore, PTCH1-mutated tumors had higher proportions of CD8 + T cells, activated NK cells, and M1 type macrophage infiltration, as well as elevated gene signatures of several steps in the cancer-immunity cycle. Notably, the PTCH1 mutation was correlated with tumor mutational burden (TMB), loss of heterozygosity score, and copy number variation burden. Our results show that the mutation of PTCH1 is a potential biomarker for predicting the response of CRC patients to immunotherapy.

• Biomarker
• Colorectal cancer
• Immune checkpoint inhibitors
• PTCH1

• tumour biomarkers
• gastrointestinal cancer
• cancer microenvironment

• The National Key Research and Development Program of China (2017YFC1308900), The Beijing Municipal Science and Technology Commission Program (Z141107002514013)
• The National Key Research and Development Program of China (2018YFC1313302) The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (No.XXT19)

• age
• gene mutation
• head and neck cancer
• immune microenvironment
• immunotherapy
• predictor

• Biomarker
• Cancer
• Immune checkpoint therapy
• PD-1
• PD-L1

• Colorectal cancer
• colon adenocarcinoma
• immune checkpoint inhibitors
• microsatellite instability
• rectum adenocarcinoma
• tumor microenvironment

• Colorectal cancer
• Immune landscape
• Immune-related genes
• Prognostic signature
• Tumor mutation burden

• TP53
• bioinformatic analysis
• bladder cancer (BLCA)
• immune checkpoint inhibitors (ICIs)
• mutant form of TP53 (TP53-MT)
• prognostic factor

• Adult
• Aged
• Aged, 80 and over
• Antigen Presentation/genetics
• Antigens, Neoplasm/immunology
• Biomarkers, Tumor/genetics
• Chemokine CXCL10/genetics
• Chemokine CXCL9/genetics
• DNA Copy Number Variations
• DNA Mutational Analysis
• Datasets as Topic
• Drug Resistance, Neoplasm/genetics
• Drug Resistance, Neoplasm/immunology
• Female
• Gene Expression Regulation, Neoplastic/immunology
• Humans
• Immune Checkpoint Inhibitors/pharmacology
• Immune Checkpoint Inhibitors/therapeutic use
• Male
• Middle Aged
• Mutation
• Neoplasm Recurrence, Local/epidemiology
• Neoplasm Recurrence, Local/genetics
• Precision Medicine/methods
• Prognosis
• Progression-Free Survival
• Retrospective Studies
• Tumor Suppressor Protein p53/genetics
• Tumor Suppressor Protein p53/metabolism
• Urinary Bladder Neoplasms/drug therapy
• Urinary Bladder Neoplasms/genetics
• Urinary Bladder Neoplasms/immunology
• Urinary Bladder Neoplasms/mortality