PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer
Abstract 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 transcr...
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Nature Portfolio
2021
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oai:doaj.org-article:af1b22a145e34167b4094d6666a0d50f2021-12-02T17:12:17ZPD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer10.1038/s41598-021-92530-32045-2322https://doaj.org/article/af1b22a145e34167b4094d6666a0d50f2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92530-3https://doaj.org/toc/2045-2322Abstract 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.Naoya OzawaTakehiko YokoboriKatsuya OsoneChika KatayamaKunihiko SugaChika KomineYuta ShibasakiTakuya ShiraishiTakuhisa OkadaRyuji KatoHiroomi OgawaAkihiko SanoMakoto SakaiMakoto SohdaHitoshi OjimaTatsuya MiyazakiYoko MotegiMunenori IdeTakashi YaoHiroyuki KuwanoKen ShirabeHiroshi SaekiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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DOAJ |
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DOAJ |
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EN |
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Medicine R Science Q |
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Medicine R Science Q Naoya Ozawa Takehiko Yokobori Katsuya Osone Chika Katayama Kunihiko Suga Chika Komine Yuta Shibasaki Takuya Shiraishi Takuhisa Okada Ryuji Kato Hiroomi Ogawa Akihiko Sano Makoto Sakai Makoto Sohda Hitoshi Ojima Tatsuya Miyazaki Yoko Motegi Munenori Ide Takashi Yao Hiroyuki Kuwano Ken Shirabe Hiroshi Saeki PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer |
| description |
Abstract 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 |
article |
| author |
Naoya Ozawa Takehiko Yokobori Katsuya Osone Chika Katayama Kunihiko Suga Chika Komine Yuta Shibasaki Takuya Shiraishi Takuhisa Okada Ryuji Kato Hiroomi Ogawa Akihiko Sano Makoto Sakai Makoto Sohda Hitoshi Ojima Tatsuya Miyazaki Yoko Motegi Munenori Ide Takashi Yao Hiroyuki Kuwano Ken Shirabe Hiroshi Saeki |
| author_facet |
Naoya Ozawa Takehiko Yokobori Katsuya Osone Chika Katayama Kunihiko Suga Chika Komine Yuta Shibasaki Takuya Shiraishi Takuhisa Okada Ryuji Kato Hiroomi Ogawa Akihiko Sano Makoto Sakai Makoto Sohda Hitoshi Ojima Tatsuya Miyazaki Yoko Motegi Munenori Ide Takashi Yao Hiroyuki Kuwano Ken Shirabe Hiroshi Saeki |
| author_sort |
Naoya Ozawa |
| title |
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_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_sort |
pd-l1 upregulation is associated with activation of the dna double-strand break repair pathway in patients with colitic cancer |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/af1b22a145e34167b4094d6666a0d50f |
| work_keys_str_mv |
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1718381455323693056 |