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PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer
Ulcerative colitis (UC) is a DNA damage-associated chronic inflammatory disease; the DNA double-strand break (DSB) repair pathway participates in UC-associated dysplasia/colitic cancer carcinogenesis. The DSB/interferon regulatory factor-1 (IRF-1) pathway can induce PD-L1 expression transcriptionall...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219733/ https://www.ncbi.nlm.nih.gov/pubmed/34158547 http://dx.doi.org/10.1038/s41598-021-92530-3 |
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author | Ozawa, Naoya Yokobori, Takehiko Osone, Katsuya Katayama, Chika Suga, Kunihiko Komine, Chika Shibasaki, Yuta Shiraishi, Takuya Okada, Takuhisa Kato, Ryuji Ogawa, Hiroomi Sano, Akihiko Sakai, Makoto Sohda, Makoto Ojima, Hitoshi Miyazaki, Tatsuya Motegi, Yoko Ide, Munenori Yao, Takashi Kuwano, Hiroyuki Shirabe, Ken Saeki, Hiroshi |
author_facet | Ozawa, Naoya Yokobori, Takehiko Osone, Katsuya Katayama, Chika Suga, Kunihiko Komine, Chika Shibasaki, Yuta Shiraishi, Takuya Okada, Takuhisa Kato, Ryuji Ogawa, Hiroomi Sano, Akihiko Sakai, Makoto Sohda, Makoto Ojima, Hitoshi Miyazaki, Tatsuya Motegi, Yoko Ide, Munenori Yao, Takashi Kuwano, Hiroyuki Shirabe, Ken Saeki, Hiroshi |
author_sort | Ozawa, Naoya |
collection | PubMed |
description | Ulcerative colitis (UC) is a DNA damage-associated chronic inflammatory disease; the DNA double-strand break (DSB) repair pathway participates in UC-associated dysplasia/colitic cancer carcinogenesis. The DSB/interferon regulatory factor-1 (IRF-1) pathway can induce PD-L1 expression transcriptionally. However, the association of PD-L1/DSB/IRF-1 with sporadic colorectal cancer (SCRC), and UC-associated dysplasia/colitic cancer, remains elusive. Therefore, we investigated the significance of the PD-L1/DSB repair pathway using samples from 17 SCRC and 12 UC patients with rare UC-associated dysplasia/colitic cancer cases by immunohistochemical analysis. We compared PD-L1 expression between patients with SCRC and UC-associated dysplasia/colitic cancer and determined the association between PD-L1 and the CD8+ T-cell/DSB/IRF-1 axis in UC-associated dysplasia/colitic cancer. PD-L1 expression in UC and UC-associated dysplasia/colitic cancer was higher than in normal mucosa or SCRC, and in CD8-positive T lymphocytes in UC-associated dysplasia/colitic cancer than in SCRC. Moreover, PD-L1 upregulation was associated with γH2AX (DSB marker) and IRF-1 upregulation in UC-associated dysplasia/colitic cancer. IRF-1 upregulation was associated with γH2AX upregulation in UC-associated dysplasia/colitic cancer but not in SCRC. Multicolour immunofluorescence staining validated γH2AX/IRF-1/PD-L1 co-expression in colitic cancer tissue sections. Thus, immune cell-induced inflammation might activate the DSB/IRF-1 axis, potentially serving as the primary regulatory mechanism of PD-L1 expression in UC-associated carcinogenesis. |
format | Online Article Text |
id | pubmed-8219733 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-82197332021-06-24 PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer Ozawa, Naoya Yokobori, Takehiko Osone, Katsuya Katayama, Chika Suga, Kunihiko Komine, Chika Shibasaki, Yuta Shiraishi, Takuya Okada, Takuhisa Kato, Ryuji Ogawa, Hiroomi Sano, Akihiko Sakai, Makoto Sohda, Makoto Ojima, Hitoshi Miyazaki, Tatsuya Motegi, Yoko Ide, Munenori Yao, Takashi Kuwano, Hiroyuki Shirabe, Ken Saeki, Hiroshi Sci Rep Article Ulcerative colitis (UC) is a DNA damage-associated chronic inflammatory disease; the DNA double-strand break (DSB) repair pathway participates in UC-associated dysplasia/colitic cancer carcinogenesis. The DSB/interferon regulatory factor-1 (IRF-1) pathway can induce PD-L1 expression transcriptionally. However, the association of PD-L1/DSB/IRF-1 with sporadic colorectal cancer (SCRC), and UC-associated dysplasia/colitic cancer, remains elusive. Therefore, we investigated the significance of the PD-L1/DSB repair pathway using samples from 17 SCRC and 12 UC patients with rare UC-associated dysplasia/colitic cancer cases by immunohistochemical analysis. We compared PD-L1 expression between patients with SCRC and UC-associated dysplasia/colitic cancer and determined the association between PD-L1 and the CD8+ T-cell/DSB/IRF-1 axis in UC-associated dysplasia/colitic cancer. PD-L1 expression in UC and UC-associated dysplasia/colitic cancer was higher than in normal mucosa or SCRC, and in CD8-positive T lymphocytes in UC-associated dysplasia/colitic cancer than in SCRC. Moreover, PD-L1 upregulation was associated with γH2AX (DSB marker) and IRF-1 upregulation in UC-associated dysplasia/colitic cancer. IRF-1 upregulation was associated with γH2AX upregulation in UC-associated dysplasia/colitic cancer but not in SCRC. Multicolour immunofluorescence staining validated γH2AX/IRF-1/PD-L1 co-expression in colitic cancer tissue sections. Thus, immune cell-induced inflammation might activate the DSB/IRF-1 axis, potentially serving as the primary regulatory mechanism of PD-L1 expression in UC-associated carcinogenesis. Nature Publishing Group UK 2021-06-22 /pmc/articles/PMC8219733/ /pubmed/34158547 http://dx.doi.org/10.1038/s41598-021-92530-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ozawa, Naoya Yokobori, Takehiko Osone, Katsuya Katayama, Chika Suga, Kunihiko Komine, Chika Shibasaki, Yuta Shiraishi, Takuya Okada, Takuhisa Kato, Ryuji Ogawa, Hiroomi Sano, Akihiko Sakai, Makoto Sohda, Makoto Ojima, Hitoshi Miyazaki, Tatsuya Motegi, Yoko Ide, Munenori Yao, Takashi Kuwano, Hiroyuki Shirabe, Ken Saeki, Hiroshi PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer |
title | PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer |
title_full | PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer |
title_fullStr | PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer |
title_full_unstemmed | PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer |
title_short | PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer |
title_sort | pd-l1 upregulation is associated with activation of the dna double-strand break repair pathway in patients with colitic cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219733/ https://www.ncbi.nlm.nih.gov/pubmed/34158547 http://dx.doi.org/10.1038/s41598-021-92530-3 |
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