P0292 CD8+ Cell Dominance in Immune Checkpoint Inhibitor-Induced Colitis and Its Heterogeneity Across Endoscopic Features
Authors: Hwang S W , Kim M K , Son H N , Hong S W , Park S H , Yang D H , Ye B D , Byeon J S , Myung S J , Yang S K , Yoon S 
Published: January 2025

Abstract

Background
Immune checkpoint inhibitor (ICI)-induced colitis is one of the major immune-related adverse events associated with ICI therapy, and it is known to be related to increased cytotoxic T cell (Tc) activity.1,2 ICI-induced colitis can be classified into Crohn’s disease (CD)-like, ulcerative colitis (UC)-like, and microscopic colitis (MC)-like patterns based on their endoscopic appearance.3 We aimed to compare T cell subsets based on the endoscopic features of ICI-induced colitis and to compare these findings with inflammatory bowel disease (IBD).

Methods
We analysed 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 of were analysed, and the immune cell profiles were compared based on their endoscopic features and further contrasted with those of IBD patients.

Results
Seventeen patients with ICI-induced colitis were included in the study. Most of these patients presented with common terminology criteria for adverse events grade 2 or higher adverse events, specifically diarrhoea (14/17, 82.4%) and colitis (12/17, 70.6%). Eleven patients (64.7%) received oral or intravenous steroid therapy (excluding beclomethasone), while six patients (35.3%) were prescribed beclomethasone. All patients showed clinical improvement after treatment. (Table 1) Based on endoscopic features, the patients were classified as CD-like (n=3, 17.6%), UC-like (n=9, 52.9%), and MC-like (n=5, 29.4%). In ICI-induced colitis, Tc was dominant over helper T cells (Th) (p=0.053), and this dominance was statistically significant in MC-like subgroup (p=0.020). On the contrary, IBD showed Th dominance(p=0.077). The number of intraepithelial CD8+ cells within the field were significantly higher in the MC-like group compared to the CD-like group (p=0.016), and similarly elevated in the UC-like group compared to the CD-like group (p=0.008). When comparing the number of intraepithelial CD8+ cells infiltrating the crypts, MC-like and UC-like subtypes had significantly more infiltrating cells than the CD-like subtype (p=0.016 and p=0.008, respectively) (Figure 1).

Conclusion
Analysis of T cell subsets of ICI-induced colitis patients revealed Tc dominant profile, contrasting with the Th dominance of IBD patients. Tc dominant profile was evident in UC-like and MC-like subtypes with marked crypt infiltration by CD8+ cells, suggesting a role for Tc in the pathophysiology of ICI-induced colitis.

References
1.Luoma AM, Suo S, Williams HL, et al. Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy. Cell. 2020;182:655-671.e22.
2.Sasson SC, Slevin SM, Cheung VTF, et al. Interferon-Gamma-Producing CD8(+) Tissue Resident Memory T Cells Are a Targetable Hallmark of Immune Checkpoint Inhibitor-Colitis. Gastroenterology. 2021;161:1229-1244.e9.
3.Abu-Sbeih H, Ali FS, Luo W, et al. Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis. J Immunother Cancer. 2018;6:95.