HLA Class I Expression Is Associated with DNA Damage and Immune Cell Infiltration into Dysplastic and Neoplastic Lesions in Ulcerative Colitis

• Published in: International journal of molecular sciences Vol. 24; no. 17; p. 13648
• Main Authors: Okami, Haruka, Ozawa, Naoya, Sohda, Makoto, Yokobori, Takehiko, Osone, Katsuya, Erkhem-Ochir, Bilguun, Dorjkhorloo, Gendensuren, Shiraishi, Takuya, Okada, Takuhisa, Sano, Akihiko, Sakai, Makoto, Miyazaki, Tatsuya, Ogawa, Hiroomi, Yao, Takashi, Oike, Takahiro, Sato, Hiro, Shirabe, Ken, Shibata, Atsushi, Saeki, Hiroshi
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2023; MDPI
• Subjects: Anti-inflammatory agents; Antigen presentation; Antimitotic agents; Antineoplastic agents; Cancer; Cancer therapies; Cells; colitic cancer; Colon; Colorectal cancer; Cytotoxicity; DNA; DNA damage; Genetic aspects; Genetic research; Histocompatibility antigens; HLA histocompatibility antigens; human leukocyte antigen; immune cells; Immunohistochemistry; Inflammation; Inflammatory bowel disease; Lymphocytes; Medical colleges; Medical research; Proteins; T cells; Tumors; Ulcerative colitis; Japan
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241713648

Human leukocyte antigen class I (HLA-I) is considered a genetic pathogen for ulcerative colitis (UC). This study aimed to investigate the significance of DNA damage and HLA-I expression in infiltrating immune cells and immune checkpoint protein PD-L1 expression in dysplasia/colitic cancer (CC) and sporadic colorectal cancer (SCRC). We performed immunohistochemical staining for HLA-I, PD-L1, γH2AX (DNA damage marker), and immune cell markers such as CD8, FOXP3, CD68, and CD163 (in surgically resected specimens from 17 SCRC patients with 12 adjacent normal mucosa (NM) and 9 UC patients with 18 dysplasia/CC tumors. The ratio of membrane HLA-I-positive epithelial cells in UC and dysplasia/CC tissues was significantly higher than that in NM and SCRC. High HLA-I expression in dysplasia/CC was associated with high positivity of γH2AX and PD-L1 expression compared to SCRC. The infiltration of CD8-positive T cells and CD68-positive macrophages in HLA-I-high dysplasia/CC was significantly higher than in UC and SCRC. Dysplasia/CC specimens with DNA damage exhibited high levels of HLA-I-positive epithelial cells with high CD8- and CD68-positive immune cell infiltration compared to UC and SCRC specimens. Targeting DNA damage in UC may regulate immune cell infiltration, immune checkpoint proteins, and carcinogenesis by modulating DNA damage-induced HLA-I antigen presentation.