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.