Anti-integrin αvβ6 autoantibodies are a potential biomarker for ulcerative colitis-like immune checkpoint inhibitor-induced colitis

• Published in: British journal of cancer Vol. 130; no. 9; pp. 1552 - 1560
• Main Authors: Yokode, Masataka, Shiokawa, Masahiro, Kawakami, Hisato, Kuwada, Takeshi, Nishikawa, Yoshihiro, Muramoto, Yuya, Kitamoto, Hiroki, Okabe, Makoto, Yamazaki, Hajime, Okamoto, Norihiro, Morita, Toshihiro, Ohno, Kazuya, Nakanishi, Risa, Takimoto, Ikuhisa, Yasuda, Muneji, Chikugo, Koki, Matsumoto, Shimpei, Yoshida, Hiroyuki, Ota, Sakiko, Nakamura, Takeharu, Okada, Hirokazu, Hirano, Tomonori, Kakiuchi, Nobuyuki, Matsumori, Tomoaki, Yamamoto, Shuji, Uza, Norimitsu, Ooi, Makoto, Kodama, Yuzo, Chiba, Tsutomu, Hayashi, Hidetoshi, Seno, Hiroshi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.05.2024; Nature Publishing Group
• Subjects: 631/154/53/2421; 631/250/38; Autoantibodies; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer Research; Drug Resistance; Endoscopy; Epidemiology; Immune checkpoint inhibitors; Inflammatory bowel disease; Molecular Medicine; Oncology; Ulcerative colitis
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-024-02647-1

Background No specific biomarker for immune checkpoint inhibitor (ICI)-induced colitis has been established. Previously, we identified anti-integrin αvβ6 autoantibodies in >90% of patients with ulcerative colitis (UC). Given that a subset of ICI-induced colitis is similar to UC, we aimed to clarify the relationship between such autoantibodies and ICI-induced colitis. Methods Serum anti-integrin αvβ6 autoantibody levels were compared between 26 patients with ICI-induced colitis and 157 controls. Endoscopic images of ICI-induced colitis were centrally reviewed. Characteristics of anti-integrin αvβ6 autoantibodies in the ICI-induced colitis patients were compared with those of UC patients. Results Anti-integrin αvβ6 autoantibodies were found in 8/26 (30.8%) patients with ICI-induced colitis and 3/157 (1.9%) controls ( P  < 0.001). Patients with anti-integrin αvβ6 autoantibodies had significantly more typical UC endoscopic features than those without the autoantibodies ( P  < 0.001). Anti-integrin αvβ6 autoantibodies in ICI-induced colitis patients were associated with grade ≥3 colitis ( P  = 0.001) and steroid resistance ( P  = 0.005). Anti-integrin αvβ6 autoantibody titers correlated with ICI-induced colitis disease activity. Anti-integrin αvβ6 autoantibodies of ICI-induced colitis exhibited similar characteristics to those of UC. Conclusions Anti-integrin αvβ6 autoantibodies may serve as potential biomarkers for the diagnosis, classification, risk management, and monitoring the disease activity, of ICI-induced colitis.