Min Kyu Kim, Hye-Nam Son, Seung Wook Hong, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Shinkyo Yoon, Sung Wook Hwang
{"title":"CD8+细胞在免疫检查点抑制剂诱导的结肠炎中的优势及其在内镜下的异质性","authors":"Min Kyu Kim, Hye-Nam Son, Seung Wook Hong, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Shinkyo Yoon, Sung Wook Hwang","doi":"10.1177/17562848241309445","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitor (ICI)-induced colitis is a significant adverse event associated with ICI therapy, known to be linked to increased cytotoxic T-cell activity.</p><p><strong>Objectives: </strong>To compare T-cell subsets based on the endoscopic features of ICI-induced colitis and to compare these findings with those of inflammatory bowel disease (IBD).</p><p><strong>Design: </strong>Prospective cohort study.</p><p><strong>Methods: </strong>We analyzed patients with ICI-induced colitis, confirmed through both endoscopic and histological evaluation. Biopsy specimens were examined using multiplex immunohistochemistry to assess their immune cell profile. Clinical outcomes were analyzed. Immune cell profiles were compared based on their endoscopic features and contrasted with those of patients with IBD.</p><p><strong>Results: </strong>Seventeen patients with ICI-induced colitis were included in the study. All patients showed clinical improvement after treatment, and steroids were administered to 11 patients (64.7%). Based on endoscopic features, the patients were classified as Crohn's disease (CD)-like (<i>n</i> = 3, 17.6%), ulcerative colitis (UC)-like (<i>n</i> = 9, 52.9%), or microscopic colitis (MC)-like (<i>n</i> = 5, 29.4%). In ICI-induced colitis, cytotoxic T cells (Tc cells) were more predominant than helper T cells (Th cells) (<i>p</i> = 0.053), and this trend was most pronounced in the MC-like subtype (<i>p</i> = 0.020). When comparing the number of CD8+ cells infiltrating the crypts, both the UC-like and MC-like subtypes had significantly more infiltrating cells than the CD-like subtype (<i>p</i> = 0.008 and <i>p</i> = 0.016, respectively). In comparison to IBD, IBD exhibited a Th-dominant profile, whereas CD-like ICI-induced colitis had a lower Th cell density than CD (<i>p</i> = 0.032) and UC-like ICI-induced colitis had a higher Tc density than UC (<i>p</i> = 0.045).</p><p><strong>Conclusion: </strong>Analysis of T-cell subsets of ICI-induced colitis revealed a Tc-dominant profile, contrasting with the Th dominance observed in patients with IBD. The Tc-dominant profile was evident in UC-like and MC-like subtypes, with significant crypt infiltration by CD8+ cells. Tc may play an important role in the pathophysiology of ICI-induced colitis.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":"17 ","pages":"17562848241309445"},"PeriodicalIF":3.9000,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672375/pdf/","citationCount":"0","resultStr":"{\"title\":\"CD8+ cell dominance in immune checkpoint inhibitor-induced colitis and its heterogeneity across endoscopic features.\",\"authors\":\"Min Kyu Kim, Hye-Nam Son, Seung Wook Hong, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Shinkyo Yoon, Sung Wook Hwang\",\"doi\":\"10.1177/17562848241309445\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Immune checkpoint inhibitor (ICI)-induced colitis is a significant adverse event associated with ICI therapy, known to be linked to increased cytotoxic T-cell activity.</p><p><strong>Objectives: </strong>To compare T-cell subsets based on the endoscopic features of ICI-induced colitis and to compare these findings with those of inflammatory bowel disease (IBD).</p><p><strong>Design: </strong>Prospective cohort study.</p><p><strong>Methods: </strong>We analyzed patients with ICI-induced colitis, confirmed through both endoscopic and histological evaluation. Biopsy specimens were examined using multiplex immunohistochemistry to assess their immune cell profile. Clinical outcomes were analyzed. Immune cell profiles were compared based on their endoscopic features and contrasted with those of patients with IBD.</p><p><strong>Results: </strong>Seventeen patients with ICI-induced colitis were included in the study. All patients showed clinical improvement after treatment, and steroids were administered to 11 patients (64.7%). Based on endoscopic features, the patients were classified as Crohn's disease (CD)-like (<i>n</i> = 3, 17.6%), ulcerative colitis (UC)-like (<i>n</i> = 9, 52.9%), or microscopic colitis (MC)-like (<i>n</i> = 5, 29.4%). In ICI-induced colitis, cytotoxic T cells (Tc cells) were more predominant than helper T cells (Th cells) (<i>p</i> = 0.053), and this trend was most pronounced in the MC-like subtype (<i>p</i> = 0.020). When comparing the number of CD8+ cells infiltrating the crypts, both the UC-like and MC-like subtypes had significantly more infiltrating cells than the CD-like subtype (<i>p</i> = 0.008 and <i>p</i> = 0.016, respectively). In comparison to IBD, IBD exhibited a Th-dominant profile, whereas CD-like ICI-induced colitis had a lower Th cell density than CD (<i>p</i> = 0.032) and UC-like ICI-induced colitis had a higher Tc density than UC (<i>p</i> = 0.045).</p><p><strong>Conclusion: </strong>Analysis of T-cell subsets of ICI-induced colitis revealed a Tc-dominant profile, contrasting with the Th dominance observed in patients with IBD. The Tc-dominant profile was evident in UC-like and MC-like subtypes, with significant crypt infiltration by CD8+ cells. Tc may play an important role in the pathophysiology of ICI-induced colitis.</p>\",\"PeriodicalId\":48770,\"journal\":{\"name\":\"Therapeutic Advances in Gastroenterology\",\"volume\":\"17 \",\"pages\":\"17562848241309445\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-12-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672375/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Gastroenterology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17562848241309445\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17562848241309445","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
CD8+ cell dominance in immune checkpoint inhibitor-induced colitis and its heterogeneity across endoscopic features.
Background: Immune checkpoint inhibitor (ICI)-induced colitis is a significant adverse event associated with ICI therapy, known to be linked to increased cytotoxic T-cell activity.
Objectives: To compare T-cell subsets based on the endoscopic features of ICI-induced colitis and to compare these findings with those of inflammatory bowel disease (IBD).
Design: Prospective cohort study.
Methods: We analyzed patients with ICI-induced colitis, confirmed through both endoscopic and histological evaluation. Biopsy specimens were examined using multiplex immunohistochemistry to assess their immune cell profile. Clinical outcomes were analyzed. Immune cell profiles were compared based on their endoscopic features and contrasted with those of patients with IBD.
Results: Seventeen patients with ICI-induced colitis were included in the study. All patients showed clinical improvement after treatment, and steroids were administered to 11 patients (64.7%). Based on endoscopic features, the patients were classified as Crohn's disease (CD)-like (n = 3, 17.6%), ulcerative colitis (UC)-like (n = 9, 52.9%), or microscopic colitis (MC)-like (n = 5, 29.4%). In ICI-induced colitis, cytotoxic T cells (Tc cells) were more predominant than helper T cells (Th cells) (p = 0.053), and this trend was most pronounced in the MC-like subtype (p = 0.020). When comparing the number of CD8+ cells infiltrating the crypts, both the UC-like and MC-like subtypes had significantly more infiltrating cells than the CD-like subtype (p = 0.008 and p = 0.016, respectively). In comparison to IBD, IBD exhibited a Th-dominant profile, whereas CD-like ICI-induced colitis had a lower Th cell density than CD (p = 0.032) and UC-like ICI-induced colitis had a higher Tc density than UC (p = 0.045).
Conclusion: Analysis of T-cell subsets of ICI-induced colitis revealed a Tc-dominant profile, contrasting with the Th dominance observed in patients with IBD. The Tc-dominant profile was evident in UC-like and MC-like subtypes, with significant crypt infiltration by CD8+ cells. Tc may play an important role in the pathophysiology of ICI-induced colitis.
期刊介绍：
Therapeutic Advances in Gastroenterology is an open access journal which delivers the highest quality peer-reviewed original research articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of gastrointestinal and hepatic disorders. The journal has a strong clinical and pharmacological focus and is aimed at an international audience of clinicians and researchers in gastroenterology and related disciplines, providing an online forum for rapid dissemination of recent research and perspectives in this area.
The editors welcome original research articles across all areas of gastroenterology and hepatology.
The journal publishes original research articles and review articles primarily. Original research manuscripts may include laboratory, animal or human/clinical studies – all phases. Letters to the Editor and Case Reports will also be considered.
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