Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in Melanoma.

Background: Neoantigens are presented on the cancer cell surface by peptide-restricted human leukocyte antigen (HLA) proteins and can subsequently activate cognate T cells. It has been hypothesized that the observed somatic mutations in tumors are shaped by immunosurveillance.
Methods: We investigated all somatic mutations identified in The Cancer Genome Atlas (TCGA) Skin Cutaneous Melanoma (SKCM) samples. By applying a computational algorithm, we calculated the binding affinity of the resulting neo-peptides and their corresponding wild-type peptides with the major histocompatibility complex (MHC) Class I complex. We then examined the relationship between binding affinity alterations and mutation frequency.
Results: Our results show that neoantigens derived from recurrent mutations tend to have lower binding affinities with the MHC Class I complex compared to peptides from non-recurrent mutations. Tumor samples harboring recurrent SKCM mutations exhibited lower immune infiltration levels, indicating a relatively colder immune microenvironment.
Conclusions: These results suggested that the occurrences of somatic mutations in melanoma have been shaped by immunosurveillance. Mutations that lead to neoantigens with high MHC class I binding affinity are more likely to be eliminated and thus are less likely to be present in tumors.
Competing Interests: Author C-CC was employed by the company Chempartner Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Jiang, Schaafsma, Hong, Zhao, Zhu, Chao and Cheng.)