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A targetable type III immune response with increase of IL-17A expressing CD4 + T cells is associated with immunotherapy-induced toxicity in melanoma.
- Source :
-
Nature cancer [Nat Cancer] 2024 Sep; Vol. 5 (9), pp. 1390-1408. Date of Electronic Publication: 2024 Aug 29. - Publication Year :
- 2024
-
Abstract
- Immune checkpoint inhibitors are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events. Proteomic analyses and multiplex cytokine and chemokine assays from serum at baseline and at the adverse event onset indicated aberrant T cell activity with differential expression of type I and III immune signatures. This was in line with the finding of an increase in the proportion of CD4 <superscript>+</superscript> T cells with IL-17A expression at the adverse event onset in the peripheral blood using flow cytometry. Multiplex immunohistochemistry and spatial transcriptomics on immunotherapy-induced skin rash and colitis showed an increase in the proportion of CD4 <superscript>+</superscript> T cells with IL-17A expression. Anti-IL-17A was administered in two patients with mild myocarditis, colitis and skin rash with resolution of the adverse events. This study highlights the potential role of type III CD4 <superscript>+</superscript> T cells in adverse event development and provides proof-of-principle evidence for a clinical trial using anti-IL-17A for treating adverse events.<br /> (© 2024. The Author(s).)
Details
- Language :
- English
- ISSN :
- 2662-1347
- Volume :
- 5
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Nature cancer
- Publication Type :
- Academic Journal
- Accession number :
- 39210005
- Full Text :
- https://doi.org/10.1038/s43018-024-00810-4