Landscape mapping of shared antigenic epitopes and their cognate tcrs of tumor-infiltrating T lymphocytes in Melanoma

Kenji Murata; Munehide Nakatsugawa; Muhammed A. Rahman; Linh T. Nguyen; Douglas G. Millar; David T. Mulder; Kenji Sugata; Hiroshi Saijo; Yukiko Matsunaga; Yuki Kagoya; Tingxi Guo; Mark Anczurowski; Chung Hsi Wang; Brian D. Burt; Dalam Ly; Kayoko Saso; Alexandra Easson; David P. Goldstein; Michael Reedijk; Danny A. Ghazarian; Trevor J. Pugh; Marcus O. Butler; Tak W. Mak; Pamela S. Ohashi; Naoto Hirano

doi:10.7554/eLife.53244

Landscape mapping of shared antigenic epitopes and their cognate tcrs of tumor-infiltrating T lymphocytes in Melanoma

Kenji Murata, Munehide Nakatsugawa, Muhammed A. Rahman, Linh T. Nguyen, Douglas G. Millar, David T. Mulder, Kenji Sugata, Hiroshi Saijo, Yukiko Matsunaga, Yuki Kagoya, Tingxi Guo, Mark Anczurowski, Chung Hsi Wang, Brian D. Burt, Dalam Ly, Kayoko Saso, Alexandra Easson, David P. Goldstein, Michael Reedijk, Danny A. GhazarianTrevor J. Pugh, Marcus O. Butler, Tak W. Mak, Pamela S. Ohashi, Naoto Hirano

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/eLife.53244
Publication status	Published - 2020 Apr
Externally published	Yes

ASJC Scopus subject areas

Neuroscience(all)
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.7554/eLife.53244

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Murata, K., Nakatsugawa, M., Rahman, M. A., Nguyen, L. T., Millar, D. G., Mulder, D. T., Sugata, K., Saijo, H., Matsunaga, Y., Kagoya, Y., Guo, T., Anczurowski, M., Wang, C. H., Burt, B. D., Ly, D., Saso, K., Easson, A., Goldstein, D. P., Reedijk, M., ... Hirano, N. (2020). Landscape mapping of shared antigenic epitopes and their cognate tcrs of tumor-infiltrating T lymphocytes in Melanoma. eLife, 9. https://doi.org/10.7554/eLife.53244

Murata, K, Nakatsugawa, M, Rahman, MA, Nguyen, LT, Millar, DG, Mulder, DT, Sugata, K, Saijo, H, Matsunaga, Y, Kagoya, Y, Guo, T, Anczurowski, M, Wang, CH, Burt, BD, Ly, D, Saso, K, Easson, A, Goldstein, DP, Reedijk, M, Ghazarian, DA, Pugh, TJ, Butler, MO, Mak, TW, Ohashi, PS & Hirano, N 2020, 'Landscape mapping of shared antigenic epitopes and their cognate tcrs of tumor-infiltrating T lymphocytes in Melanoma', eLife, vol. 9. https://doi.org/10.7554/eLife.53244

@article{07302acec2f845e4b3432769e7ec02e6,

title = "Landscape mapping of shared antigenic epitopes and their cognate tcrs of tumor-infiltrating T lymphocytes in Melanoma",

abstract = "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.",

author = "Kenji Murata and Munehide Nakatsugawa and Rahman, {Muhammed A.} and Nguyen, {Linh T.} and Millar, {Douglas G.} and Mulder, {David T.} and Kenji Sugata and Hiroshi Saijo and Yukiko Matsunaga and Yuki Kagoya and Tingxi Guo and Mark Anczurowski and Wang, {Chung Hsi} and Burt, {Brian D.} and Dalam Ly and Kayoko Saso and Alexandra Easson and Goldstein, {David P.} and Michael Reedijk and Ghazarian, {Danny A.} and Pugh, {Trevor J.} and Butler, {Marcus O.} and Mak, {Tak W.} and Ohashi, {Pamela S.} and Naoto Hirano",

note = "Funding Information: This work was supported by Funding Information: Researchers and a Guglietti Fellowship (YK); the Province of Ontario (TG, MA); and the Natural Funding Information: We thank the Princess Margaret Melanoma/Skin Oncology Disease Site, BioBank, and Cell Production Team for collecting melanoma samples and generating TILs. This work was supported by an Ontario Institute for Cancer Research Clinical Investigator Award IA-039 (NH); the Terry Fox immunotherapy NeTwork (iTNT) Program (PSO, NH); the Princess Margaret Cancer Centre Innovation Accelerator Fund (NH); the Princess Margaret Cancer Foundation (NH, MOB); the Mitacs Internship (KM); a Japan Society for the Promotion of Science Postdoctoral Fellowship for Overseas Researchers and a Guglietti Fellowship (YK); the Province of Ontario (TG, MA); and the Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarship (TG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2020, eLife Sciences Publications Ltd. All rights reserved.",

year = "2020",

month = apr,

doi = "10.7554/eLife.53244",

language = "English",

volume = "9",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - Landscape mapping of shared antigenic epitopes and their cognate tcrs of tumor-infiltrating T lymphocytes in Melanoma

AU - Murata, Kenji

AU - Nakatsugawa, Munehide

AU - Rahman, Muhammed A.

AU - Nguyen, Linh T.

AU - Millar, Douglas G.

AU - Mulder, David T.

AU - Sugata, Kenji

AU - Saijo, Hiroshi

AU - Matsunaga, Yukiko

AU - Kagoya, Yuki

AU - Guo, Tingxi

AU - Anczurowski, Mark

AU - Wang, Chung Hsi

AU - Burt, Brian D.

AU - Ly, Dalam

AU - Saso, Kayoko

AU - Easson, Alexandra

AU - Goldstein, David P.

AU - Reedijk, Michael

AU - Ghazarian, Danny A.

AU - Pugh, Trevor J.

AU - Butler, Marcus O.

AU - Mak, Tak W.

AU - Ohashi, Pamela S.

AU - Hirano, Naoto

N1 - Funding Information: This work was supported by Funding Information: Researchers and a Guglietti Fellowship (YK); the Province of Ontario (TG, MA); and the Natural Funding Information: We thank the Princess Margaret Melanoma/Skin Oncology Disease Site, BioBank, and Cell Production Team for collecting melanoma samples and generating TILs. This work was supported by an Ontario Institute for Cancer Research Clinical Investigator Award IA-039 (NH); the Terry Fox immunotherapy NeTwork (iTNT) Program (PSO, NH); the Princess Margaret Cancer Centre Innovation Accelerator Fund (NH); the Princess Margaret Cancer Foundation (NH, MOB); the Mitacs Internship (KM); a Japan Society for the Promotion of Science Postdoctoral Fellowship for Overseas Researchers and a Guglietti Fellowship (YK); the Province of Ontario (TG, MA); and the Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarship (TG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2020, eLife Sciences Publications Ltd. All rights reserved.

PY - 2020/4

Y1 - 2020/4

N2 - 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.

AB - 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.

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U2 - 10.7554/eLife.53244

DO - 10.7554/eLife.53244

M3 - Article

C2 - 32314731

AN - SCOPUS:85084356122

SN - 2050-084X

VL - 9

JO - eLife

JF - eLife

ER -

Landscape mapping of shared antigenic epitopes and their cognate tcrs of tumor-infiltrating T lymphocytes in Melanoma

Abstract

ASJC Scopus subject areas

UN SDGs

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