Background: RNA modification is one of the epigenetic mechanisms that regulates post-transcriptional gene expression, and abnormal RNA modifications have been reported to play important roles in tumorigenesis. N7-methylguanosine (m7G) is an essential modification at the 5′ cap of human mRNA. However, a systematic and pan-cancer analysis of the clinical relevance of m7G related regulatory genes is still lacking.Methods: We used univariate Cox model and Kaplan-Meier analysis to generate the forest plot of OS, PFI, DSS and identified the correlation between the altered expression of m7G regulators and patient survival in 33 cancer types from the TCGA and GTEx databases. Then, the “estimate” R-package, ssGSEA and CIBERSORT were used to depict the pan-cancer immune landscape. Through Spearman’s correlation test, we analyzed the correlation between m7G regulators and the tumor microenvironment (TME), immune subtype, and drug sensitivity of the tumors, which was further validated in NSCLC. We also assessed the changes in the expression of m7G related regulatory genes in NSCLC with regards to the genetic and transcriptional aspects and evaluated the correlation of METTL1 and WDR4 expression with TMB, MSI and immunotherapy in pan-cancer.Results: High expression of most of the m7G regulators was significantly associated with worse prognosis. Correlation analyses revealed that the expression of majority of the m7G regulators was correlated with tumor immune infiltration and tumor stem cell scores. Drug sensitivity analysis showed that the expression of CYFP1,2 was closely related to drug sensitivity for various anticancer agents (p < 0.001). Analysis of the pan-cancer immune subtype revealed significant differences in the expression of m7G regulators between different immune subtypes (p < 0.001). Additionally, the types and proportions of mutations in METTL1 and WDR4 and their relevance to immunotherapy were further described.Conclusion: Our study is the first to evaluate the correlation between the altered expression of m7G regulators and patient survival, the degree of immune infiltration, TME and drug sensitivity in pan-cancer datasets.

Emerging evidence indicates that the induction of radiotherapy(RT) on the immunogenic cell death (ICD) is not only dependent on its direct cytotoxic effect, changes in the tumor immune microenvironment also play an important role in it. Tumor immune microenvironment (TIME) refers to the immune microenvironment that tumor cells exist, including tumor cells, inflammatory cells, immune cells, various signaling molecules and extracellular matrix. TIME has a barrier effect on the anti-tumor function of immune cells, which can inhibit all stages of anti-tumor immune response. The remodeling of TIME caused by RT may affect the degree of immunogenicity, and make it change from immunosuppressive phenotype to immunostimulatory phenotype. It is of great significance to reveal the causes of immune escape of tumor cells, especially for the treatment of drug-resistant tumor. In this review, we focus on the effect of RT on the TIME, the mechanism of RT in reversing the TIME to suppress intrinsic immunity, and the sensitization effect of the remodeling of TIME caused by RT on the effectiveness of immunotherapy.