biostudies-literatureUnknown12(11)Wang QImmunotherapies have dramatically improved survival outcome for patients with melanoma. <i>MUC16</i> encodes cancer antigen 125 (CA125), which is frequently mutated in melanoma. In this study, we correlated the <i>MUC16</i> 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 <i>MUC16</i> 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 <i>MUC16</i> mutations. Immune-suppressive M2 macrophages were enriched in patients with wild-type <i>MUAging10827-10843https://www.ebi.ac.uk/biostudies/studies/S-EPMC7346065biostudies-literatureHigh mutation load, immune-activated microenvironment, favorable outcome, and better immunotherapeutic efficacy in melanoma patients harboring <i>MUC16</i>/CA125 mutations.PMC7346065Li XYang YWang QChen KYang MfalseHigh mutation load, immune-activated microenvironment, favorable outcome, and better immunotherapeutic efficacy in melanoma patients harboring <i>MUC16</i>/CA125 mutations.Immunotherapies have dramatically improved survival outcome for patients with melanoma. <i>MUC16</i> encodes cancer antigen 125 (CA125), which is frequently mutated in melanoma. In this study, we correlated the <i>MUC16</i> 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 <i>MUC16</i> 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 <i>MUC16</i> mutations. Immune-suppressive M2 macrophages were enriched in patients with wild-type <i>MU2020-01-01T00:00:00Z2020 Jun2025-04-22T19:33:43.161Z2025-04-06T02:49:10.444ZS-EPMC73460653249199510.18632/aging.103296