Immune profile of metastatic uveal melanoma during treatment with pembrolizumab

9536 Background: Metastatic uveal melanoma (mUM) is a rare and aggressive disease. No standard therapy has been established. All the available treatments derive from trials in cutaneous melanoma. A minority of patients with mUM can benefit from immunotherapy. Immunological features of a group of patients with metastatic UM treated with Pembrolizumab were analyzed in order to explore the immune-response in this disease and the potential factors able to select the patients who can benefit from immunotherapy. Methods: Blood samples from 12 UM patients before (T0) and during treatment with Pembrolizumab (T1: after 1 cycle of Pembrolizumab; T2: after 3 cycle of Pembrolizumab) were collected. Peripheral blood mononucleated cells (PBMCs) were isolated and characterized for markers expression. Sera were analyzed for a panel of soluble (s) immune checkpoints and cytokines. The correlation between immunological parameters with PFS and OS was explored. Blood samples from 6 metastatic cutaneous melanoma (CM) patients with a confirmed response to anti PD-1 agents were also collected during the treatment and analyzed for PBMCs and sera. Results: Soluble CTLA4, sPD-L1, sCD137, sTIM3 were significantly higher in UM than in CM. CD137 was significantly higher in UM patients progressed with Pembrolizumab than in the 2 responsive patients (512 pg/ml vs < 12.9 pg/ml, respectively, p = 0.04) who are still alive and on treatment after a median follow-up of 24 months. Low sGITR, sCD137, sHVEM, and sTIM3 are associated with longer PFS. IL-8 was lower in CM than UM (2.5 pg/ml vs 40.7 pg/ml) and in the responsive versus progressed UM patients (3,7 pg/ml vs 118 pg/ml, p = 0,042). Low levels of IL-8 and IL-1-alpha are significantly associated with longer PFS (p = 0.011 and 0.010 respectively). In responsive patients CD137 expression on CD3+, CD4+ and CD8+ T cells was higher than in progressed patients, while sCD137 was absent. Conclusions: A group of s-immune checkpoints and cytokines correlate with Pembrolizumab effectiveness in mUM. High expression of CD137 on T cells associated with the absence of its soluble form in responders could suggest the correlation between the retention of this co-stimulatory molecule and efficacy of anti-PD1.