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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-...

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Detalles Bibliográficos
Autores principales: 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
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
Descripción
Sumario: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.