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Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma
It is important to evaluate the clinical importance of both CD8 T cells and CD4 T cells expression simultaneously because they have crucial networks in tumour targeting immune responses. In 97 RCC patients, RNA sequencing and gene set enrichment analysis of both CD8 and CD4 T cells based on the expr...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148296/ https://www.ncbi.nlm.nih.gov/pubmed/32277125 http://dx.doi.org/10.1038/s41598-020-63060-1 |
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author | Kawashima, Atsunari Kanazawa, Takayuki Kidani, Yujiro Yoshida, Tetsuya Hirata, Michinari Nishida, Kentaro Nojima, Satoshi Yamamoto, Yoshiyuki Kato, Taigo Hatano, Koji Ujike, Takeshi Nagahara, Akira Fujita, Kazutoshi Morimoto-Okazawa, Akiko Iwahori, Kota Uemura, Motohide Imamura, Ryoichi Ohkura, Naganari Morii, Eiichi Sakaguchi, Shimon Wada, Hisashi Nonomura, Norio |
author_facet | Kawashima, Atsunari Kanazawa, Takayuki Kidani, Yujiro Yoshida, Tetsuya Hirata, Michinari Nishida, Kentaro Nojima, Satoshi Yamamoto, Yoshiyuki Kato, Taigo Hatano, Koji Ujike, Takeshi Nagahara, Akira Fujita, Kazutoshi Morimoto-Okazawa, Akiko Iwahori, Kota Uemura, Motohide Imamura, Ryoichi Ohkura, Naganari Morii, Eiichi Sakaguchi, Shimon Wada, Hisashi Nonomura, Norio |
author_sort | Kawashima, Atsunari |
collection | PubMed |
description | It is important to evaluate the clinical importance of both CD8 T cells and CD4 T cells expression simultaneously because they have crucial networks in tumour targeting immune responses. In 97 RCC patients, RNA sequencing and gene set enrichment analysis of both CD8 and CD4 T cells based on the expression levels of PD-1 and TIM-3 implied that the populations of PD-1+TIM-3+ CD8 T cells and PD-1lowTIM-3 + CD4 T cells were characterized as exhausted CD8 T cells and regulatory CD4 T cells, respectively. These populations of CD4 and CD8 T cells were significantly upregulated in the patients with RCC of higher WHO/ISUP grade (grades 3, 4) (P < 0.001). Moreover, the cytokine productivities of each population in both CD4 and CD8 T cells of the higher-grade patients were significantly lower than those of the lower-grade patients (P < 0.05). Multivariate analysis showed the prognosis of patients with metastatic RCC of higher WHO/ISUP grade treated by nivolumab to be significantly worse than that of patients with lower grade (P = 0.026). This study showed that tumour grade significantly correlated with dysfunction of both CD4+ and CD8+ TILs and the efficacy of nivolumab treatment. |
format | Online Article Text |
id | pubmed-7148296 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71482962020-04-15 Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma Kawashima, Atsunari Kanazawa, Takayuki Kidani, Yujiro Yoshida, Tetsuya Hirata, Michinari Nishida, Kentaro Nojima, Satoshi Yamamoto, Yoshiyuki Kato, Taigo Hatano, Koji Ujike, Takeshi Nagahara, Akira Fujita, Kazutoshi Morimoto-Okazawa, Akiko Iwahori, Kota Uemura, Motohide Imamura, Ryoichi Ohkura, Naganari Morii, Eiichi Sakaguchi, Shimon Wada, Hisashi Nonomura, Norio Sci Rep Article It is important to evaluate the clinical importance of both CD8 T cells and CD4 T cells expression simultaneously because they have crucial networks in tumour targeting immune responses. In 97 RCC patients, RNA sequencing and gene set enrichment analysis of both CD8 and CD4 T cells based on the expression levels of PD-1 and TIM-3 implied that the populations of PD-1+TIM-3+ CD8 T cells and PD-1lowTIM-3 + CD4 T cells were characterized as exhausted CD8 T cells and regulatory CD4 T cells, respectively. These populations of CD4 and CD8 T cells were significantly upregulated in the patients with RCC of higher WHO/ISUP grade (grades 3, 4) (P < 0.001). Moreover, the cytokine productivities of each population in both CD4 and CD8 T cells of the higher-grade patients were significantly lower than those of the lower-grade patients (P < 0.05). Multivariate analysis showed the prognosis of patients with metastatic RCC of higher WHO/ISUP grade treated by nivolumab to be significantly worse than that of patients with lower grade (P = 0.026). This study showed that tumour grade significantly correlated with dysfunction of both CD4+ and CD8+ TILs and the efficacy of nivolumab treatment. Nature Publishing Group UK 2020-04-10 /pmc/articles/PMC7148296/ /pubmed/32277125 http://dx.doi.org/10.1038/s41598-020-63060-1 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 Kawashima, Atsunari Kanazawa, Takayuki Kidani, Yujiro Yoshida, Tetsuya Hirata, Michinari Nishida, Kentaro Nojima, Satoshi Yamamoto, Yoshiyuki Kato, Taigo Hatano, Koji Ujike, Takeshi Nagahara, Akira Fujita, Kazutoshi Morimoto-Okazawa, Akiko Iwahori, Kota Uemura, Motohide Imamura, Ryoichi Ohkura, Naganari Morii, Eiichi Sakaguchi, Shimon Wada, Hisashi Nonomura, Norio Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma |
title | Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma |
title_full | Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma |
title_fullStr | Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma |
title_full_unstemmed | Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma |
title_short | Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma |
title_sort | tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148296/ https://www.ncbi.nlm.nih.gov/pubmed/32277125 http://dx.doi.org/10.1038/s41598-020-63060-1 |
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