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

Front Immunol. 2022 Jan 17:12:703821. doi: 10.3389/fimmu.2021.703821. eCollection 2021.


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.

Keywords: Melanoma; antigen presentation; immunosurveillance; neoantigen; recurrent mutation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antigens, Neoplasm / immunology
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immunologic Surveillance / immunology*
  • Immunotherapy / methods
  • Melanoma / immunology*
  • Melanoma, Cutaneous Malignant
  • Mutation / immunology*
  • Mutation Rate
  • Peptides / immunology
  • Skin Neoplasms / immunology*
  • T-Lymphocytes / immunology*
  • Tumor Microenvironment / immunology


  • Antigens, Neoplasm
  • Histocompatibility Antigens Class I
  • Peptides