摘要：SummaryElimination of cancerous cells by the immune system is an important mechanism of protection from cancer, however, its effectiveness can be reduced owing to development of resistance and evasion. To understand the systemic immune response in advanced untreated primary colorectal cancer, we analyze immune subtypes and immune evasion via neoantigen-related mechanisms. We identify a distinctive cancer subtype characterized by immune evasion and very poor overall survival. This subtype has less clonal highly expressed neoantigens and high chromosomal instability, resulting in adaptive immune resistance mediated by the immune checkpoint molecules and neoantigen presentation disorders. We also observe that neoantigen depletion caused by immunoediting and high clonal neoantigen load are correlated with a good overall survival. Our results indicate that the status of the tumor microenvironment and neoantigen composition are promising new prognostic biomarkers with potential relevance for treatment plan decisions in advanced CRC.Graphical abstractDisplay OmittedHighlights•Patients with advanced colorectal cancer have a distinctive immunological feature•Immunoediting status and clonal neoantigens are prognostic for overall survival•Neoantigen-mediated immune evasion patterns provide evidence of past immune attacks•Clonality and high expression are factors characteristic of immunogenic neoantigensMolecular biology; Immune system; Genomics
