Abstract B18: Induction of Th1/Th17 and inhibition of Th3 cellular profile by DC-based immunotherapy is associated with immunological and clinical anti-tumor responses in melanoma patients

Abstract

Abstract The ability of DCs to induce a primary immune response makes them ideal candidates for cancer vaccines against tumors. Recently, in a serie of phase I/II clinical studies, we showed the effectiveness of autologous DCs loaded with a conditioned allogeneic melanoma cell lysate named TRIMEL. Our results demonstrated a correlation between positive tumor-specific delayed type hypersensitivity (DTH) reaction induced by DC-vaccination, and improved long-term patient survival in late-stage melanoma patients. In fact, 60% of patients showed a positive DTH reaction showing a three-fold prolonged survival compared to non-responder patients (33 and 11 months respectively). Herein, we investigated whether cellular and cytokine profiles in patients PBL before and after vaccination reflects differential responses associated to the clinical outcome. Analysis of T cell populations in blood showed that melanoma patients (n=28) have an increased proportion of Th3 (CD4+TGF-β+) regulatory T lymphocytes (2.64 % ± 0.16) compared to normal donors (n=14) (1.72 % ± 0.22). However, we didn't observed differences in TGF-β concentrations at serum level. Moreover, we analyzed vaccine effect on cytokine and cellular responses in PBL. Interestling, although there was not differences in Th3 population proportions between responder (n=14) and non-responder patients (n=14) before vaccination, after treatment responder patients showed a three-fold reduction of CD4+TGf-β+ T cells compared to non-responders (1.65 % ± 0.19 and 5.54 % ± 0.28 respectively). Furthermore, our results show that DC-vaccination resulted in a three-fold augment of IFN-γ releasing by Th1 population and a two-fold increase of IL-17 producing Th17 lymphocyte population in responder patients, but not in non-responders. A direct correlation between IFN-γ and IL-17 production in responder patients blood was observed (p < 0.0001) suggesting that those cytokines may favour an anti melanoma response. Taken together our results indicates that despite undetectable differences in the cellular and cytokine profiles in melanoma patients before DC-vaccination, immunization resulted in two different pattern of response associated to the immunological and clinical outcome. Our study may contribute to a better understanding of clinical immunological responses and to an earlier prognosis of patient outcome. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B18