Cargando…

Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors

Indications for current immune checkpoint inhibitors are expanding and now include thymic epithelial tumors (TETs). Although clinical trials on immune checkpoint inhibitors for TETs are ongoing, a rationale has not yet been established for immunotherapy for TETs. Therefore, we herein performed pheno...

Descripción completa

Detalles Bibliográficos
Autores principales: Yamamoto, Yoko, Iwahori, Kota, Funaki, Soichiro, Matsumoto, Mitsunobu, Hirata, Michinari, Yoshida, Tetsuya, Kanzaki, Ryu, Kanou, Takashi, Ose, Naoko, Minami, Masato, Sato, Eiichi, Kumanogoh, Atsushi, Shintani, Yasushi, Okumura, Meinoshin, Wada, Hisashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055333/
https://www.ncbi.nlm.nih.gov/pubmed/32132638
http://dx.doi.org/10.1038/s41598-020-61053-8
_version_ 1783503355133296640
author Yamamoto, Yoko
Iwahori, Kota
Funaki, Soichiro
Matsumoto, Mitsunobu
Hirata, Michinari
Yoshida, Tetsuya
Kanzaki, Ryu
Kanou, Takashi
Ose, Naoko
Minami, Masato
Sato, Eiichi
Kumanogoh, Atsushi
Shintani, Yasushi
Okumura, Meinoshin
Wada, Hisashi
author_facet Yamamoto, Yoko
Iwahori, Kota
Funaki, Soichiro
Matsumoto, Mitsunobu
Hirata, Michinari
Yoshida, Tetsuya
Kanzaki, Ryu
Kanou, Takashi
Ose, Naoko
Minami, Masato
Sato, Eiichi
Kumanogoh, Atsushi
Shintani, Yasushi
Okumura, Meinoshin
Wada, Hisashi
author_sort Yamamoto, Yoko
collection PubMed
description Indications for current immune checkpoint inhibitors are expanding and now include thymic epithelial tumors (TETs). Although clinical trials on immune checkpoint inhibitors for TETs are ongoing, a rationale has not yet been established for immunotherapy for TETs. Therefore, we herein performed phenotypic and functional analyses of T cells in surgically resected TET tissues with a focus on the anti-tumor properties of T cells to TETs as a step towards establishing a rationale for immunotherapy for TETs. We examined T-cell profiles in surgically resected TET tissues, particularly CD4 and CD8 single-positive T cells, using flow cytometry. In the functional analysis of T cells in TETs, we investigated not only cytokine production by T cells, but also their cytotoxicity using bispecific T-cell engager technology. The cluster analysis of T-cell profiles based on flow cytometric data revealed that type B3 thymoma and thymic carcinoma (B3/C) belonged to the hot cluster characterized by a high proportion of Tim-3+ and CD103+ in CD4 and CD8 single-positive T cells. Enhancements in cytokine production and the cytotoxicity of T cells by the anti-PD-1 antibody were significantly greater in B3/C. These results indicate the potential of immunotherapy for patients with B3/C.
format Online
Article
Text
id pubmed-7055333
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-70553332020-03-12 Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors Yamamoto, Yoko Iwahori, Kota Funaki, Soichiro Matsumoto, Mitsunobu Hirata, Michinari Yoshida, Tetsuya Kanzaki, Ryu Kanou, Takashi Ose, Naoko Minami, Masato Sato, Eiichi Kumanogoh, Atsushi Shintani, Yasushi Okumura, Meinoshin Wada, Hisashi Sci Rep Article Indications for current immune checkpoint inhibitors are expanding and now include thymic epithelial tumors (TETs). Although clinical trials on immune checkpoint inhibitors for TETs are ongoing, a rationale has not yet been established for immunotherapy for TETs. Therefore, we herein performed phenotypic and functional analyses of T cells in surgically resected TET tissues with a focus on the anti-tumor properties of T cells to TETs as a step towards establishing a rationale for immunotherapy for TETs. We examined T-cell profiles in surgically resected TET tissues, particularly CD4 and CD8 single-positive T cells, using flow cytometry. In the functional analysis of T cells in TETs, we investigated not only cytokine production by T cells, but also their cytotoxicity using bispecific T-cell engager technology. The cluster analysis of T-cell profiles based on flow cytometric data revealed that type B3 thymoma and thymic carcinoma (B3/C) belonged to the hot cluster characterized by a high proportion of Tim-3+ and CD103+ in CD4 and CD8 single-positive T cells. Enhancements in cytokine production and the cytotoxicity of T cells by the anti-PD-1 antibody were significantly greater in B3/C. These results indicate the potential of immunotherapy for patients with B3/C. Nature Publishing Group UK 2020-03-04 /pmc/articles/PMC7055333/ /pubmed/32132638 http://dx.doi.org/10.1038/s41598-020-61053-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yamamoto, Yoko
Iwahori, Kota
Funaki, Soichiro
Matsumoto, Mitsunobu
Hirata, Michinari
Yoshida, Tetsuya
Kanzaki, Ryu
Kanou, Takashi
Ose, Naoko
Minami, Masato
Sato, Eiichi
Kumanogoh, Atsushi
Shintani, Yasushi
Okumura, Meinoshin
Wada, Hisashi
Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors
title Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors
title_full Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors
title_fullStr Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors
title_full_unstemmed Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors
title_short Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors
title_sort immunotherapeutic potential of cd4 and cd8 single-positive t cells in thymic epithelial tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055333/
https://www.ncbi.nlm.nih.gov/pubmed/32132638
http://dx.doi.org/10.1038/s41598-020-61053-8
work_keys_str_mv AT yamamotoyoko immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT iwahorikota immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT funakisoichiro immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT matsumotomitsunobu immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT hiratamichinari immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT yoshidatetsuya immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT kanzakiryu immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT kanoutakashi immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT osenaoko immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT minamimasato immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT satoeiichi immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT kumanogohatsushi immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT shintaniyasushi immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT okumurameinoshin immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors
AT wadahisashi immunotherapeuticpotentialofcd4andcd8singlepositivetcellsinthymicepithelialtumors