High mutation load, immune-activated microenvironment, favorable outcome, and better immunotherapeutic efficacy in melanoma patients harboring MUC16/CA125 mutations.

ABSTRACT: Immunotherapies have dramatically improved survival outcome for patients with melanoma. MUC16 encodes cancer antigen 125 (CA125), which is frequently mutated in melanoma. In this study, we correlated the MUC16 mutational status with the following: tumor mutation burden (TML), multiple immune-related signals in microenvironment, deregulated pathways, survival outcome, and immunotherapeutic efficacy. We found that patients with MUC16 mutations had significantly higher TML than those without it. Enriched pro-inflammatory CD8 T cells and M1 macrophages, enhanced interferon gamma (IFNγ) and T cell-inflamed signatures, and increased cytolytic activity were associated with MUC16 mutations. Immune-suppressive M2 macrophages were enriched in patients with wild-type MU

SUBMITTER: Wang Q 

PROVIDER: S-EPMC7346065 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature