Naturally Occurring Telomerase-Specific CD4 T-Cell Immunity in Melanoma.

ABSTRACT CD4 T cells play a key role in anticancer immunity. Here, we investigate the clinical relevance of circulating CD4 Th1 response against telomerase (anti-TERT Th1 response) in melanoma patients. The spontaneous anti-TERT Th1 response was detected in 54.5% (85/156) of melanoma patients before treatment. The prevalence of this systemic response was inversely related to Breslow thickness above 1mm and AJCC stage ≥ II (P = 0.001 and 0.032). In contrast to patients treated by targeted therapies, the anti-TERT Th1 immunity was associated with objective response after immune checkpoint inhibitors (ICI) treatment. Hence 86% (18/21) of responder patients exhibited pre-existing anti-TERT Th1 versus 35% (6/19) in non-responders (P = 0.001). This response was also associated with increased progression free survival and overall survival in melanoma patients treated with ICI (P = 0.0008 and 0.012 respectively). Collectively, the presence of circulating anti-TERT Th1 response is inversely related to melanoma evolution and appears to be a predictive factor of response to immunotherapy. Our results highlight the interest of telomerase-specific CD4 Th1 response as a promising blood based biomarker of immune checkpoint inhibitors therapy in melanoma.