In the past years immune checkpoint Inhibitors (ICI), more specifically the PD-1 and CTLA-4 Inhibitors have become a go-to therapy of advanced melanoma. The outcome of the patients receiving ICI improved significantly. Unfortunately, some of them developed a more or less severe autoimmune reaction to this medication, also known as immune related adverse event (irAE). The aim of this study is to have a closer look at the ICI-induced changes within the CD4+ T-cells and try to see their role in the irAEs. We observed and collected peripheral blood mononuclear cells from patients with melanoma stage III and IV for the first four months of receiving ICI. Immunotherapy-naivety was the main inclusion requirement. The gating strategy for the analysis with fluorescence cytometry was based on the surface markers specific for the T-helper and T-regulatory cells and CLA as a specific marker for skin memory T cells. 21 patients (mean age 73) receiving either PD-1 or PD-1 and CTLA-4 Inhibitors were recruited. A total of 4 patients developed irAEs (1 Myositis, 1 Colitis, 1 Nepritis and 1 elevated Lipase). Our initial observation shows a steady increase of the CLA expression and a convert from t-follicular to t-non follicular cells as the CXCR5-expression of the T-cells decreases in the early phase of the therapy. The comparison between patients who developed irAEs and those who did not suggests that T-regulatory cells may play a role in irAEs as there is a strong increase in their population among the first mentioned group. So far, we could establish that the T-cells are influenced by the ICI as there are changes in the same direction among the majority of the patients. In the next months, we want to recruit at least ten more patients and closer study and define the impact of the therapy on the individual T-helper cell subsets.

ESDR289 - The effect of immune checkpoint Inhibitors on the CD4+ T-cell population by patients with advanced melanoma and the role of these cells in immune related adverse events

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING