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Somatic gene mutations were found not only to elicit adaptive immunity but also to influence the composition of tumor immune microenvironment and various processes of antitumor immunity. However, due to an incomplete view of associations between gene mutations and immunophenotypes, how tumor cells shape the immune microenvironment and further determine the clinical benefit of immunotherapy is still unclear. To address this, we proposed a computational approach, inference of mutation effect on immunophenotype by integrated gene set enrichment analysis (MEIGSEA), for tracing back the genomic factor responsible for differences in immunophenotypes. MEIGSEA was demonstrated to accurately identify the previous confirmed immune-associated gene mutations, and systematic evaluation in simulation data further supported its performance. We used MEIGSEA to investigate the influence of driver gene mutations on the infiltration of 22 immune cell types across 19 cancers from The Cancer Genome Atlas. The top associated gene mutations with infiltration of CD8 T cells, such as CASP8, KRAS and EGFR, also showed extensive impact on other immune components; meanwhile, immune effector cells shared critical gene mutations that collaboratively contribute to shaping distinct tumor immune microenvironment. Furthermore, we highlighted the predictive capacity of gene mutations that are positively associated with CD8 T cells for the clinical benefit of immunotherapy. Taken together, we present a computational framework to help illustrate the potential of somatic gene mutations in shaping the tumor immune microenvironment.<\/jats:p>","DOI":"10.1093\/bib\/bbac064","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T13:30:33Z","timestamp":1644931833000},"source":"Crossref","is-referenced-by-count":10,"title":["Revealing the contribution of somatic gene mutations to shaping tumor immune microenvironment"],"prefix":"10.1093","volume":"23","author":[{"given":"Liwen","family":"Xu","sequence":"first","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, 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