Cargando…
Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma
HLA-restricted T cell responses can induce antitumor effects in cancer patients. Previous human T cell research has largely focused on the few HLA alleles prevalent in a subset of ethnic groups. Here, using a panel of newly developed peptide-exchangeable peptide/HLA multimers and artificial antigen-...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234812/ https://www.ncbi.nlm.nih.gov/pubmed/32314731 http://dx.doi.org/10.7554/eLife.53244 |
_version_ | 1783535850176380928 |
---|---|
author | Murata, Kenji Nakatsugawa, Munehide Rahman, Muhammed A Nguyen, Linh T Millar, Douglas G Mulder, David T Sugata, Kenji Saijo, Hiroshi Matsunaga, Yukiko Kagoya, Yuki Guo, Tingxi Anczurowski, Mark Wang, Chung-Hsi Burt, Brian D Ly, Dalam Saso, Kayoko Easson, Alexandra Goldstein, David P Reedijk, Michael Ghazarian, Danny Pugh, Trevor J Butler, Marcus O Mak, Tak W Ohashi, Pamela S Hirano, Naoto |
author_facet | Murata, Kenji Nakatsugawa, Munehide Rahman, Muhammed A Nguyen, Linh T Millar, Douglas G Mulder, David T Sugata, Kenji Saijo, Hiroshi Matsunaga, Yukiko Kagoya, Yuki Guo, Tingxi Anczurowski, Mark Wang, Chung-Hsi Burt, Brian D Ly, Dalam Saso, Kayoko Easson, Alexandra Goldstein, David P Reedijk, Michael Ghazarian, Danny Pugh, Trevor J Butler, Marcus O Mak, Tak W Ohashi, Pamela S Hirano, Naoto |
author_sort | Murata, Kenji |
collection | PubMed |
description | HLA-restricted T cell responses can induce antitumor effects in cancer patients. Previous human T cell research has largely focused on the few HLA alleles prevalent in a subset of ethnic groups. Here, using a panel of newly developed peptide-exchangeable peptide/HLA multimers and artificial antigen-presenting cells for 25 different class I alleles and greater than 800 peptides, we systematically and comprehensively mapped shared antigenic epitopes recognized by tumor-infiltrating T lymphocytes (TILs) from eight melanoma patients for all their class I alleles. We were able to determine the specificity, on average, of 12.2% of the TILs recognizing a mean of 3.1 shared antigen-derived epitopes across HLA-A, B, and C. Furthermore, we isolated a number of cognate T cell receptor genes with tumor reactivity. Our novel strategy allows for a more complete examination of the immune response and development of novel cancer immunotherapy not limited by HLA allele prevalence or tumor mutation burden. |
format | Online Article Text |
id | pubmed-7234812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-72348122020-05-20 Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma Murata, Kenji Nakatsugawa, Munehide Rahman, Muhammed A Nguyen, Linh T Millar, Douglas G Mulder, David T Sugata, Kenji Saijo, Hiroshi Matsunaga, Yukiko Kagoya, Yuki Guo, Tingxi Anczurowski, Mark Wang, Chung-Hsi Burt, Brian D Ly, Dalam Saso, Kayoko Easson, Alexandra Goldstein, David P Reedijk, Michael Ghazarian, Danny Pugh, Trevor J Butler, Marcus O Mak, Tak W Ohashi, Pamela S Hirano, Naoto eLife Immunology and Inflammation HLA-restricted T cell responses can induce antitumor effects in cancer patients. Previous human T cell research has largely focused on the few HLA alleles prevalent in a subset of ethnic groups. Here, using a panel of newly developed peptide-exchangeable peptide/HLA multimers and artificial antigen-presenting cells for 25 different class I alleles and greater than 800 peptides, we systematically and comprehensively mapped shared antigenic epitopes recognized by tumor-infiltrating T lymphocytes (TILs) from eight melanoma patients for all their class I alleles. We were able to determine the specificity, on average, of 12.2% of the TILs recognizing a mean of 3.1 shared antigen-derived epitopes across HLA-A, B, and C. Furthermore, we isolated a number of cognate T cell receptor genes with tumor reactivity. Our novel strategy allows for a more complete examination of the immune response and development of novel cancer immunotherapy not limited by HLA allele prevalence or tumor mutation burden. eLife Sciences Publications, Ltd 2020-04-21 /pmc/articles/PMC7234812/ /pubmed/32314731 http://dx.doi.org/10.7554/eLife.53244 Text en © 2020, Murata et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Murata, Kenji Nakatsugawa, Munehide Rahman, Muhammed A Nguyen, Linh T Millar, Douglas G Mulder, David T Sugata, Kenji Saijo, Hiroshi Matsunaga, Yukiko Kagoya, Yuki Guo, Tingxi Anczurowski, Mark Wang, Chung-Hsi Burt, Brian D Ly, Dalam Saso, Kayoko Easson, Alexandra Goldstein, David P Reedijk, Michael Ghazarian, Danny Pugh, Trevor J Butler, Marcus O Mak, Tak W Ohashi, Pamela S Hirano, Naoto Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma |
title | Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma |
title_full | Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma |
title_fullStr | Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma |
title_full_unstemmed | Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma |
title_short | Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma |
title_sort | landscape mapping of shared antigenic epitopes and their cognate tcrs of tumor-infiltrating t lymphocytes in melanoma |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234812/ https://www.ncbi.nlm.nih.gov/pubmed/32314731 http://dx.doi.org/10.7554/eLife.53244 |
work_keys_str_mv | AT muratakenji landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT nakatsugawamunehide landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT rahmanmuhammeda landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT nguyenlinht landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT millardouglasg landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT mulderdavidt landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT sugatakenji landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT saijohiroshi landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT matsunagayukiko landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT kagoyayuki landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT guotingxi landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT anczurowskimark landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT wangchunghsi landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT burtbriand landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT lydalam landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT sasokayoko landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT eassonalexandra landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT goldsteindavidp landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT reedijkmichael landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT ghazariandanny landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT pughtrevorj landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT butlermarcuso landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT maktakw landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT ohashipamelas landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma AT hiranonaoto landscapemappingofsharedantigenicepitopesandtheircognatetcrsoftumorinfiltratingtlymphocytesinmelanoma |