Blood and tissue correlates of steroid non-response in checkpoint inhibition-induced immune-related adverse events.
1/5 보강
[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 immu
- 연구 설계 Cross-sectional
APA
van Eijs MJM, van der Wal MM, et al. (2025). Blood and tissue correlates of steroid non-response in checkpoint inhibition-induced immune-related adverse events.. Communications medicine, 5(1), 472. https://doi.org/10.1038/s43856-025-01164-3
MLA
van Eijs MJM, et al.. "Blood and tissue correlates of steroid non-response in checkpoint inhibition-induced immune-related adverse events.." Communications medicine, vol. 5, no. 1, 2025, pp. 472.
PMID
41254329 ↗
Abstract 한글 요약
[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 T1/T17 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.
[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 T1/T17 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.