A targetable type III immune response with increase of IL-17A expressing CD4$^{+}$ T cells is associated with immunotherapy-induced toxicity in melanoma
Year: 2024
Type: article
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$^{+}$ 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$^{+}$ 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$^{+}$ T cells in adverse event development and provides proof-of-principle evidence for a clinical trial using anti-IL-17A for treating adverse events.
DOI: 10.5167/uzh-262336
Authors: Dimitriou, Florentia, Cheng, Phil F, Saltari, Annalisa, Schaper-Gerhardt, Katrin, Staeger, Ramon, Haunerdinger, Veronika, Sella, Federica, Tastanova, Aizhan, Urban, Christian, Dettwiler, Susanne, Mihic-Probst, Daniela, Matter, Christian M, Michielin, Olivier, Gutzmer, Ralf, Long, Georgina V, Becher, Burkhard, Levesque, Mitchell P, Dummer, Reinhard
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6967207143
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