Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma

Verheijden, Rik J.; Burgers, Femke H.; Janssen, Josephine C.; Putker, Anouk E.; Veenstra, Sophie P.G.R.; Hospers, Geke A.P.; Aarts, Maureen J.B.; Hehenkamp, Karel W.; Doornebosch, Veerle L.E.; Verhaert, Marthe; van den Berkmortel, Franchette W.P.J.; Chatzidionysiou, Katerina; Llobell, Arturo; Barros, Milton; Maria, Alexandre T.J.; Takeji, Akari; García Morillo, José-Salvador; Lidar, Merav; van Eijs, Mick J.M.; Blank, Christian U.; Aspeslagh, Sandrine; Piersma, Djura; Kapiteijn, Ellen; Labots, Mariette; Boers-Sonderen, Marye J.; van der Veldt, Astrid A.M.; Haanen, John B.A.G.; May, Anne M.; Suijkerbuijk, Karijn P.M.

doi:10.1016/j.ejca.2024.114172

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Cited by 7 publications

References 32 publications

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Targeting molecular pathways to control immune checkpoint inhibitor toxicities

Reschke,

Sullivan,

Lipson

et al. 2024

Trends in Immunology

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Targeting molecular pathways to control immune checkpoint inhibitor toxicities

Reschke,

Sullivan,

Lipson

et al. 2024

Trends in Immunology

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Immune checkpoint inhibition of metastatic melanoma: achieving high efficacy in the face of high toxicity

Justice,

Kankaria,

Johnson

2024

Expert Review of Clinical Pharmacology

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

van Eijs,

van der Wal,

Klotškova

et al. 2024

Preprint

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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 contribute to more targeted irAE management regimens. We took a multi-omics approach to identify blood- and tissue-based predictors of steroid response and to explore underlying mechanisms of steroid non-response in irAEs. In the blood, steroid non-response correlated with trends for elevated Tc1/Tc17 CD8+ T cells and serum interleukin (IL)-17, IL-6, IL-12 and IL-23 prior to initiation of steroids, along with persistent (CD8+) T cell proliferation and activation after start of steroids. A remarkably fast decrease in inflammatory gene signatures and lymphocyte infiltration was observed in colitis tissue of steroid responders obtained within 24h after initiation of steroids. Peripheral T cell PD-1 receptor occupancy was not associated with steroid response. Colitis tissue of steroid non-responders was enriched for activated CD4+ memory T cells and a pronounced type 1/17 immune response. Together, our findings suggest rapid immunological effects of steroids in circulating cells and irAE-affected tissue and support that an enhanced type 1/type 17 response is associated with steroid non-response in irAEs.

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Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma

Cited by 7 publications

References 32 publications

Targeting molecular pathways to control immune checkpoint inhibitor toxicities

Targeting molecular pathways to control immune checkpoint inhibitor toxicities

Immune checkpoint inhibition of metastatic melanoma: achieving high efficacy in the face of high toxicity

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

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