4.5 Article

Identification of characteristic subepithelial surface granulomatosis in immune-related adverse event-associated enterocolitis

期刊

CANCER SCIENCE
卷 112, 期 3, 页码 1320-1325

出版社

WILEY
DOI: 10.1111/cas.14773

关键词

biomarker; colitis; immune checkpoint inhibitors; immune-related adverse event; subepithelial surface granulomatosis

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资金

  1. Project for Cancer Research and Therapeutic Evolution (P-CREATE) [19cm0106309h0004]
  2. Japan Agency for Medical Research and Development (AMED)

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ICIs treatment may induce enterocolitis, characterized by ulcerative colitis-like and graft vs host disease-like patterns. A new characteristic, subepithelial surface granulomatosis (SSG), observed in both patterns, could be a surrogate marker of systemic anticancer immune activation. Prospective studies with larger sample sizes are recommended for further validation.
Immune checkpoint inhibitors (ICIs) have provided an additional treatment option for various types of human cancers. However, ICIs often induce various immune-related adverse events (irAEs). Enterocolitis is a major irAE with poorly understood histopathological characteristics. In this study, we retrospectively investigated the histopathology of colon tissue samples from 17 patients treated with ICIs. There were two major histological patterns of colitis: an ulcerative colitis-like pattern and a graft vs host disease-like pattern. Although these two patterns of colitis were mutually exclusive, both patterns often showed a characteristic that we call subepithelial surface granulomatosis (SSG), which has not been reported in other types of colitis. SSG was found even in colon tissue without symptoms or endoscopic findings of colitis. Given the increasing reports of sarcoid reaction or exacerbation of tuberculosis after treatment with ICIs, granuloma formation could be a histological hallmark of systemic immune activation by ICIs. Although statistical significance was not obtained, probably because of the small sample size, SSG may be a surrogate biomarker of systemic anticancer immune activation. We propose that a prospective study with larger sample size be performed.

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