Communications medicine, Volume 5, Issue 1, 18 3 2025, Pages 472 Blood and tissue correlates of steroid non-response in checkpoint inhibition-induced immune-related adverse events. van Eijs MJM, van der Wal MM, Klotškova HB, Dautzenberg NMM, Schuiveling M, Verheijden RJ, van Schaik FDM, Oldenburg B, Nierkens S, UNICIT Consortium, Suijkerbuijk KPM, van Wijk F
Background
High-dose steroids constitute the cornerstone of first-line treatment for immune-related adverse events (irAEs) associated with immune checkpoint inhibitors, but compromise antitumor immunity. A deeper understanding of irAEs and their response to steroids can improve management.
Methods
Using a multi-omics approach, we investigated blood- and tissue-based correlates of steroid response, focusing on gastro-intestinal irAEs, in the largest cohort to date.
Results
Here we show clear trends for elevated TC1/TC17 CD8+ T cells and Th1/Th7-associated interleukins before steroid initiation, and persistent (CD8+) T cell activation after initiation of steroids in blood of steroid non-responders. Cross-sectional analysis of colitis tissue suggested lower lymphocyte infiltration within 24 h in steroid responders. Peripheral T cell PD-1 receptor occupancy was unrelated to steroid response. Non-responders' colitis tissue was enriched with activated CD4+ memory T cells and a pronounced type 1/17 immune response.
Conclusions
These findings highlight rapid steroid effects on circulating cells and irAE-affected tissue and support that an enhanced type 1/type 17 response may be associated with steroid non-response in irAEs. Validation of these findings in larger cohorts is warranted.
