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Background <p>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.</p> Methods <p>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.</p> Results <p>Here we show clear trends for elevated T<sub>C</sub>1/T<sub>C</sub>17 CD8<sup>+</sup> T cells and Th1/Th17-associated interleukins before steroid initiation, and persistent (CD8<sup>+</sup>) 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<sup>+</sup> memory T cells and a pronounced type 1/17 immune response.</p> Conclusions <p>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.</p>

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Blood and tissue correlates of steroid non-response in checkpoint inhibition-induced immune-related adverse events

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月18日

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  • Mick J. M. van Eijs,
  • M. Marlot van der Wal,
  • Hedi-Britt Klotškova,
  • Noël M. M. Dautzenberg,
  • Mark Schuiveling,
  • Rik J. Verheijden,
  • Fiona D. M. van Schaik,
  • Bas Oldenburg,
  • Stefan Nierkens,
  • Femke van Wijk,
  • Karijn P. M. Suijkerbuijk,
  • Femke van Wijk

摘要

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/Th17-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.