期刊
FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.703821
关键词
Melanoma; recurrent mutation; immunosurveillance; neoantigen; antigen presentation
类别
资金
- Cancer Prevention Research Institute of Texas (CPRIT) [RR180061]
- NCI of the NIH [1R21CA227996]
- T32 training grant of the NIH [T32 AI007363]
The study suggests that somatic mutations in melanoma may be influenced by immunosurveillance, with mutations leading to neoantigens generally having lower MHC Class I binding affinity, and tumor samples carrying recurrent SKCM mutations exhibiting lower levels of immune infiltration.
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.
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