{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T19:33:12Z","timestamp":1789414392246,"version":"build-2803163510"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RR180061"],"award-info":[{"award-number":["RR180061"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016958","name":"Office of Research Infrastructure Programs, National Institutes of Health","doi-asserted-by":"publisher","award":["1R21CA227996"],"award-info":[{"award-number":["1R21CA227996"]}],"id":[{"id":"10.13039\/100016958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.703821","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T05:00:42Z","timestamp":1642395642000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in Melanoma"],"prefix":"10.3389","volume":"12","author":[{"given":"Chongming","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien","family":"Schaafsma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanding","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Chi","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/B978-0-12-394296-8.00007-5","article-title":"Cancer Immunoediting: From Surveillance to Escape","volume":"3","author":"Teng","year":"2013","journal-title":"Cancer Immunother (Elsevier)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000386035","article-title":"The Concept of Immunological Surveillance","volume":"13","author":"Burnet","year":"1970","journal-title":"Immunol Aspects Neoplasia"},{"key":"B3","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/imm.12675","article-title":"Antigen Processing and Immune Regulation in the Response to Tumours","volume":"150","author":"Reeves","year":"2017","journal-title":"Immunology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"7175","DOI":"10.18632\/oncotarget.12739","article-title":"The Concept of Immune Surveillance Against Tumors: The First Theories","volume":"8","author":"Ribatti","year":"2017","journal-title":"Oncotarget"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.657293","article-title":"Immunometabolism at the Nexus of Cancer Therapeutic Efficacy and Resistance","volume":"12","author":"Traba","year":"2021","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.tcb.2019.01.003","article-title":"Mutational and Antigenic Landscape in Tumor Progression and Cancer Immunotherapy","volume":"29","author":"Vitale","year":"2019","journal-title":"Trends Cell Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-18-0129","article-title":"The Mutation-Associated Neoantigen Functional Expansion of Specific T Cells (Manafest) Assay: A Sensitive Platform for Monitoring Antitumor Immunity","volume":"6","author":"Danilova","year":"2018","journal-title":"Cancer Immunol Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20141308","article-title":"Genomic and Bioinformatic Profiling of Mutational Neoepitopes Reveals New Rules to Predict Anticancer Immunogenicity","volume":"211","author":"Duan","year":"2014","journal-title":"J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx687","article-title":"Differential Binding Affinity of Mutated Peptides for Mhc Class I is a Predictor of Survival in Advanced Lung Cancer and Melanoma","volume":"29","author":"Ghorani","year":"2018","journal-title":"Ann Oncol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/cr.2016.155","article-title":"Immune Targets and Neoantigens for Cancer Immunotherapy and Precision Medicine","volume":"27","author":"Wang","year":"2017","journal-title":"Cell Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12920-019-0544-1","article-title":"Elevated Neoantigen Levels in Tumors With Somatic Mutations in the Hla-a, Hla-B, Hla-C and B2m Genes","volume":"12","author":"Castro","year":"2019","journal-title":"BMC Med Genomics"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz851","article-title":"Somatic Selection Distinguishes Oncogenes and Tumor Suppressor Genes","volume":"36","author":"Chandrashekar","year":"2020","journal-title":"Bioinformatics"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.042","article-title":"Universal Patterns of Selection in Cancer and Somatic Tissues","volume":"171","author":"Martincorena","year":"2017","journal-title":"Cell"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1032-7","article-title":"Neoantigen-Directed Immune Escape in Lung Cancer Evolution","volume":"567","author":"Rosenthal","year":"2019","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13059-018-1434-0","article-title":"Negative Selection in Tumor Genome Evolution Acts on Essential Cellular Functions and the Immunopeptidome","volume":"19","author":"Zapata","year":"2018","journal-title":"Genome Biol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.cell.2014.12.033","article-title":"Molecular and Genetic Properties of Tumors Associated With Local Immune Cytolytic Activity","volume":"160","author":"Rooney","year":"2015","journal-title":"Cell"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1126\/science.1203486","article-title":"Cancer Immunoediting: Integrating Immunity\u2019s Roles in Cancer Suppression and Promotion","volume":"331","author":"Schreiber","year":"2011","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e1009368","DOI":"10.1371\/journal.pgen.1009368","article-title":"Low Immunogenicity of Common Cancer Hot Spot Mutations Resulting in False Immunogenic Selection Signals","volume":"17","author":"Claeys","year":"2021","journal-title":"PloS Genet"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0532-6","article-title":"Lack of Detectable Neoantigen Depletion Signals in the Untreated Cancer Genome","volume":"51","author":"Van den Eynden","year":"2019","journal-title":"Nat Genet"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1016\/j.cell.2021.03.009","article-title":"Characterizing Genetic Intra-Tumor Heterogeneity Across 2,658 Human Cancer Genomes","volume":"184","author":"Dentro","year":"2021","journal-title":"Cell"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.01.032","article-title":"Passenger Mutations in More Than 2,500 Cancer Genomes: Overall Molecular Functional Impact and Consequences","volume":"180","author":"Kumar","year":"2020","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1213968110","article-title":"Impact of Deleterious Passenger Mutations on Cancer Progression","volume":"110","author":"McFarland","year":"2013","journal-title":"Proc Natl Acad Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e1008227","DOI":"10.1371\/journal.pgen.1008227","article-title":"Quantifying Immune-Based Counterselection of Somatic Mutations","volume":"15","author":"Yang","year":"2019","journal-title":"PloS Genet"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.001","article-title":"Allele-Specific Hla Loss and Immune Escape in Lung Cancer Evolution","volume":"171","author":"McGranahan","year":"2017","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700893","article-title":"Netmhcpan-4.0: Improved Peptide\u2013Mhc Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data","volume":"199","author":"Jurtz","year":"2017","journal-title":"J Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.02.007","article-title":"Mass Spectrometry Profiling of Hla-Associated Peptidomes in Mono-Allelic Cells Enables More Accurate Epitope Prediction","volume":"46","author":"Abelin","year":"2017","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M114.042812","article-title":"Mass Spectrometry of Human Leukocyte Antigen Class I Peptidomes Reveals Strong Effects of Protein Abundance and Turnover on Antigen Presentation","volume":"14","author":"Bassani-Sternberg","year":"2015","journal-title":"Mol Cell Proteomics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e1253654","DOI":"10.1080\/2162402X.2016.1253654","article-title":"Identification of Genetic Determinants of Breast Cancer Immune Phenotypes by Integrative Genome-Scale Analysis","volume":"6","author":"Hendrickx","year":"2017","journal-title":"Oncoimmunology"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.050","article-title":"Mhc-I Genotype Restricts the Oncogenic Mutational Landscape","volume":"171","author":"Marty","year":"2017","journal-title":"Cell"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.11.004","article-title":"Shared Immunogenic Poly-Epitope Frameshift Mutations in Microsatellite Unstable Tumors","volume":"183","author":"Roudko","year":"2020","journal-title":"Cell"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235122","article-title":"Cancer Genome Landscapes","volume":"339","author":"Vogelstein","year":"2013","journal-title":"science"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxw026","article-title":"Targeting Neoantigens for Cancer Immunotherapy","volume":"28","author":"Lu","year":"2016","journal-title":"Int Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1314","article-title":"Driverdbv2: A Database for Human Cancer Driver Gene Research","volume":"44","author":"Chung","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"4120","DOI":"10.18632\/oncotarget.23469","article-title":"Hla Class I Loss and Pd-L1 Expression in Lung Cancer: Impact on T-Cell Infiltration and Immune Escape","volume":"9","author":"Perea","year":"2018","journal-title":"Oncotarget"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.03.007","article-title":"Genomic and Functional Approaches to Understanding Cancer Aneuploidy","volume":"33","author":"Taylor","year":"2018","journal-title":"Cancer Cell"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms3612","article-title":"Inferring Tumour Purity and Stromal and Immune Cell Admixture From Expression Data","volume":"4","author":"Yoshihara","year":"2013","journal-title":"Nat Commun"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1172\/JCI142823","article-title":"An Unbiased Approach to Defining Bona Fide Cancer Neoepitopes That Elicit Immune-Mediated Cancer Rejection","volume":"131","author":"Brennick","year":"2021","journal-title":"J Clin Invest"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1172\/jci.insight.129152","article-title":"Mass Spectrometry\u2013Driven Exploration Reveals Nuances of Neoepitope-Driven Tumor Rejection","volume":"4","author":"Ebrahimi-Nik","year":"2019","journal-title":"JCI Insight"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0559","article-title":"Tumor Immunity and Survival as a Function of Alternative Neopeptides in Human Cancer","volume":"6","author":"Rech","year":"2018","journal-title":"Cancer Immunol Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1172\/jci.insight.127239","article-title":"Cd91 on Dendritic Cells Governs Immunosurveillance of Nascent, Emerging Tumors","volume":"4","author":"Sedlacek","year":"2019","journal-title":"JCI Insight"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-020-18514-5","article-title":"The Shared Frameshift Mutation Landscape of Microsatellite-Unstable Cancers Suggests Immunoediting During Tumor Evolution","volume":"11","author":"Ballhausen","year":"2020","journal-title":"Nat Commun"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3547","article-title":"Whole-Genome Mutational Landscape and Characterization of Noncoding and Structural Mutations in Liver Cancer","volume":"48","author":"Fujimoto","year":"2016","journal-title":"Nat Genet"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.043","article-title":"Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes","volume":"172","author":"Gee","year":"2018","journal-title":"Cell"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nature22071","article-title":"Whole-Genome Landscapes of Major Melanoma Subtypes","volume":"545","author":"Hayward","year":"2017","journal-title":"Nature"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2018.06.003","article-title":"Tsnadb: A Database for Tumor-Specific Neoantigens From Immunogenomics Data Analysis","volume":"16","author":"Wu","year":"2018","journal-title":"Genomics Proteomics Bioinf"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1166","article-title":"Allele Frequency Net 2015 Update: New Features for Hla Epitopes, Kir and Disease and Hla Adverse Drug Reaction Associations","volume":"43","author":"Gonz\u00e1lez-Galarza","year":"2015","journal-title":"Nucleic Acids Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.703821\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T05:00:46Z","timestamp":1642395646000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.703821\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,17]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2021.703821"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.703821","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,17]]},"article-number":"703821"}}