Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in Melanoma
BackgroundNeoantigens 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.MethodsWe investigated al...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.703821/full |
| _version_ | 1819005094413205504 |
|---|---|
| author | Chongming Jiang Evelien Schaafsma Wei Hong Yanding Zhao Ken Zhu Cheng-Chi Chao Chao Cheng Chao Cheng Chao Cheng Chao Cheng |
| author_facet | Chongming Jiang Evelien Schaafsma Wei Hong Yanding Zhao Ken Zhu Cheng-Chi Chao Chao Cheng Chao Cheng Chao Cheng Chao Cheng |
| author_sort | Chongming Jiang |
| collection | DOAJ |
| description | BackgroundNeoantigens 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.MethodsWe 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.ResultsOur 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.ConclusionsThese 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. |
| first_indexed | 2024-12-20T23:47:19Z |
| format | Article |
| id | doaj.art-39e94ce6832542629e0c0492f60c8af4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T23:47:19Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-39e94ce6832542629e0c0492f60c8af42022-12-21T19:22:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.703821703821Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in MelanomaChongming Jiang0Evelien Schaafsma1Wei Hong2Yanding Zhao3Ken Zhu4Cheng-Chi Chao5Chao Cheng6Chao Cheng7Chao Cheng8Chao Cheng9Department of Medicine, Baylor College of Medicine, Houston, TX, United StatesDepartment of Molecular and Systems Biology, Dartmouth College, Hanover, NH, United StatesDepartment of Medicine, Baylor College of Medicine, Houston, TX, United StatesDepartment of Medicine, Baylor College of Medicine, Houston, TX, United StatesMedical School, UT Southwestern Medical Center, Dallas, TX, United StatesAntibody Discovery, Chempartner Corporation, South San Francisco, CA, United StatesDepartment of Medicine, Baylor College of Medicine, Houston, TX, United StatesDan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, United StatesDepartment of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH, United StatesThe Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, United StatesBackgroundNeoantigens 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.MethodsWe 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.ResultsOur 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.ConclusionsThese 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.703821/fullMelanomarecurrent mutationimmunosurveillanceneoantigenantigen presentation |
| spellingShingle | Chongming Jiang Evelien Schaafsma Wei Hong Yanding Zhao Ken Zhu Cheng-Chi Chao Chao Cheng Chao Cheng Chao Cheng Chao Cheng Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in Melanoma Frontiers in Immunology Melanoma recurrent mutation immunosurveillance neoantigen antigen presentation |
| title | Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in Melanoma |
| title_full | Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in Melanoma |
| title_fullStr | Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in Melanoma |
| title_full_unstemmed | Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in Melanoma |
| title_short | Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in Melanoma |
| title_sort | influence of t cell mediated immune surveillance on somatic mutation occurrences in melanoma |
| topic | Melanoma recurrent mutation immunosurveillance neoantigen antigen presentation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.703821/full |
| work_keys_str_mv | AT chongmingjiang influenceoftcellmediatedimmunesurveillanceonsomaticmutationoccurrencesinmelanoma AT evelienschaafsma influenceoftcellmediatedimmunesurveillanceonsomaticmutationoccurrencesinmelanoma AT weihong influenceoftcellmediatedimmunesurveillanceonsomaticmutationoccurrencesinmelanoma AT yandingzhao influenceoftcellmediatedimmunesurveillanceonsomaticmutationoccurrencesinmelanoma AT kenzhu influenceoftcellmediatedimmunesurveillanceonsomaticmutationoccurrencesinmelanoma AT chengchichao influenceoftcellmediatedimmunesurveillanceonsomaticmutationoccurrencesinmelanoma AT chaocheng influenceoftcellmediatedimmunesurveillanceonsomaticmutationoccurrencesinmelanoma AT chaocheng influenceoftcellmediatedimmunesurveillanceonsomaticmutationoccurrencesinmelanoma AT chaocheng influenceoftcellmediatedimmunesurveillanceonsomaticmutationoccurrencesinmelanoma AT chaocheng influenceoftcellmediatedimmunesurveillanceonsomaticmutationoccurrencesinmelanoma |