PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer
| Autor: | Yuta Shibasaki, Yoko Motegi, Makoto Sakai, Takashi Yao, Hiroshi Saeki, Munenori Ide, Takehiko Yokobori, Ryuji Kato, Katsuya Osone, Tatsuya Miyazaki, Takuhisa Okada, Ken Shirabe, Hiroyuki Kuwano, Akihiko Sano, Hitoshi Ojima, Takuya Shiraishi, Hiroomi Ogawa, Naoya Ozawa, Kunihiko Suga, Chika Komine, Chika Katayama, Makoto Sohda |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer microenvironment
Adult Male Transcriptional Activation DNA Repair Science Gene Expression Inflammation medicine.disease_cause Article B7-H1 Antigen Downregulation and upregulation PD-L1 medicine Humans DNA Breaks Double-Stranded Intestinal Mucosa Aged Multidisciplinary biology business.industry DNA Middle Aged medicine.disease Ulcerative colitis Colorectal cancer Dysplasia Surgical oncology Colonic Neoplasms Cancer research biology.protein Immunohistochemistry Tumour immunology Medicine Colitis Ulcerative Female medicine.symptom Carcinogenesis business Colorectal Neoplasms CD8 Interferon Regulatory Factor-1 |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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