Similarity and difference in tumor-infiltrating lymphocytes in original tumor tissues and those of in vitro expanded populations in head and neck cancer
Though adoptive tumor-infiltrating lymphocyte (TIL) therapy has been explored in clinical trials for many years, there is little information for the clonotype composition between TILs in original tumor tissues and TILs that were in vitro expanded and infused to cancer patients. To investigate the si...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790501/ https://www.ncbi.nlm.nih.gov/pubmed/29423084 http://dx.doi.org/10.18632/oncotarget.23454 |
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author | Ren, Lili Matsuda, Tatsuo Deng, Boya Kiyotani, Kazuma Kato, Taigo Park, Jae-Hyun Seiwert, Tanguy Y. Vokes, Everett E. Agrawal, Nishant Nakamura, Yusuke |
author_facet | Ren, Lili Matsuda, Tatsuo Deng, Boya Kiyotani, Kazuma Kato, Taigo Park, Jae-Hyun Seiwert, Tanguy Y. Vokes, Everett E. Agrawal, Nishant Nakamura, Yusuke |
author_sort | Ren, Lili |
collection | PubMed |
description | Though adoptive tumor-infiltrating lymphocyte (TIL) therapy has been explored in clinical trials for many years, there is little information for the clonotype composition between TILs in original tumor tissues and TILs that were in vitro expanded and infused to cancer patients. To investigate the similarity/difference in TILs in original tumor tissues and those of in vitro expanded populations in squamous cell carcinoma of head and neck (SCCHN) as well as their correlation with somatic mutations in cancer cells, we performed whole exome analysis, expression profile analysis of immune-related genes, and T cell receptor (TCR) analysis of original TILs and in vitro expanded TILs in 8 surgically-resected HPV-negative fresh tumors with SCCHN. We found an unusually high number of non-synonymous somatic mutations (4290, 1779 and 901 mutations) in three SCCHN tumors, in which we identified mutations in mismatch repair genes, MSH2 or MSH4, or a DNA polymerase gene, POLE. Interestingly, dominant TCR clonotypes of expanded CD8(+) TILs derived from these three tumors revealed high similarity to those in original tumors while for remaining tumors with the lower mutational load, we found that T cell clonotypes between TILs in original tumor tissues and those expanded in vitro were almost entirely different. Our findings might provide clinically useful information for identification of tumor-antigen-specific T cell clones that may lead to further improvement of adoptive TIL therapy for SCCHN patients. |
format | Online Article Text |
id | pubmed-5790501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57905012018-02-08 Similarity and difference in tumor-infiltrating lymphocytes in original tumor tissues and those of in vitro expanded populations in head and neck cancer Ren, Lili Matsuda, Tatsuo Deng, Boya Kiyotani, Kazuma Kato, Taigo Park, Jae-Hyun Seiwert, Tanguy Y. Vokes, Everett E. Agrawal, Nishant Nakamura, Yusuke Oncotarget Research Paper Though adoptive tumor-infiltrating lymphocyte (TIL) therapy has been explored in clinical trials for many years, there is little information for the clonotype composition between TILs in original tumor tissues and TILs that were in vitro expanded and infused to cancer patients. To investigate the similarity/difference in TILs in original tumor tissues and those of in vitro expanded populations in squamous cell carcinoma of head and neck (SCCHN) as well as their correlation with somatic mutations in cancer cells, we performed whole exome analysis, expression profile analysis of immune-related genes, and T cell receptor (TCR) analysis of original TILs and in vitro expanded TILs in 8 surgically-resected HPV-negative fresh tumors with SCCHN. We found an unusually high number of non-synonymous somatic mutations (4290, 1779 and 901 mutations) in three SCCHN tumors, in which we identified mutations in mismatch repair genes, MSH2 or MSH4, or a DNA polymerase gene, POLE. Interestingly, dominant TCR clonotypes of expanded CD8(+) TILs derived from these three tumors revealed high similarity to those in original tumors while for remaining tumors with the lower mutational load, we found that T cell clonotypes between TILs in original tumor tissues and those expanded in vitro were almost entirely different. Our findings might provide clinically useful information for identification of tumor-antigen-specific T cell clones that may lead to further improvement of adoptive TIL therapy for SCCHN patients. Impact Journals LLC 2017-12-19 /pmc/articles/PMC5790501/ /pubmed/29423084 http://dx.doi.org/10.18632/oncotarget.23454 Text en Copyright: © 2018 Ren et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Ren, Lili Matsuda, Tatsuo Deng, Boya Kiyotani, Kazuma Kato, Taigo Park, Jae-Hyun Seiwert, Tanguy Y. Vokes, Everett E. Agrawal, Nishant Nakamura, Yusuke Similarity and difference in tumor-infiltrating lymphocytes in original tumor tissues and those of in vitro expanded populations in head and neck cancer |
title | Similarity and difference in tumor-infiltrating lymphocytes in original tumor tissues and those of in vitro expanded populations in head and neck cancer |
title_full | Similarity and difference in tumor-infiltrating lymphocytes in original tumor tissues and those of in vitro expanded populations in head and neck cancer |
title_fullStr | Similarity and difference in tumor-infiltrating lymphocytes in original tumor tissues and those of in vitro expanded populations in head and neck cancer |
title_full_unstemmed | Similarity and difference in tumor-infiltrating lymphocytes in original tumor tissues and those of in vitro expanded populations in head and neck cancer |
title_short | Similarity and difference in tumor-infiltrating lymphocytes in original tumor tissues and those of in vitro expanded populations in head and neck cancer |
title_sort | similarity and difference in tumor-infiltrating lymphocytes in original tumor tissues and those of in vitro expanded populations in head and neck cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790501/ https://www.ncbi.nlm.nih.gov/pubmed/29423084 http://dx.doi.org/10.18632/oncotarget.23454 |
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