Research Paper Volume 12, Issue 11 pp 10827—10843
High mutation load, immune-activated microenvironment, favorable outcome, and better immunotherapeutic efficacy in melanoma patients harboring MUC16/CA125 mutations
- 1 Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
- 2 Tianjin Cancer Institute, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
Received: February 11, 2020 Accepted: April 28, 2020 Published: June 3, 2020https://doi.org/10.18632/aging.103296
How to Cite
Copyright © 2020 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 MUC16. Immune checkpoints expression (e.g., PD-L1, PD-1 and CTLA-4) was also elevated in patients with MUC16 mutations. Immune response relevant circuits were among the top enriched pathways in samples with MUC16 mutations. Patients with MUC16 mutations exhibited a significantly better prognosis. For patients who received immunotherapy, the presence of MUC16 mutations was associated with a better response rate and survival outcome in male patients but not in female or overall patients. These findings provide new implications for tailoring immunotherapeutic strategies for melanoma patients.