A novel immune classification reveals distinct immune escape mechanism and genomic alterations: implications for immunotherapy in hepatocellular carcinoma

Abstract Background The tumor immunological microenvironment (TIME) has a prominent impact on prognosis and immunotherapy. However, the heterogeneous TIME mechanisms by which affects immunotherapy have not been elucidated in hepatocellular carcinoma (HCC). Methods A total of 2195 eligible HCC patients from TCGA GEO database were collected. We comprehensively explored different phenotypes its clinical significance. potential immune escape what genomic alterations may drive formation further investigated. Results identified three HCC: TIME-1, “immune-deficiency” phenotype, with cell depletion proliferation; TIME-2, “immune-suppressed” enrichment immunosuppressive cells; TIME-3, “immune-activated phenotype”, abundant leukocytes infiltration activation. sensitivity to both sorafenib differed among phenotypes. also underlined mechanisms: lack defective antigen presentation capacity increased cells rich immunoinhibitory molecules TIME-3. demonstrated specific events: TIME-1 characterized TP53, CDKN2A, CTNNB1, AXIN1 FOXD4 alterations; TIME-2 significant alteration patterns PI3K pathway; TIME-3 ARID1A mutation. Besides, index (TI) was proposed quantify pattern, it superior prognostic predictor. pipeline developed classify single patient into one these subtypes calculated TI. Conclusions outcomes, HCC, could present strategies for improving efficacy TI as novel immunotherapeutic signature that guide personalized management HCC.