Abstract 4046: Interleukin-10 and programmed death-1 cooperate to regulate tumor antigen-specific CD8+ T cells in melanoma patients

Abstract

Abstract With the recent success of immune checkpoint blockade in the clinic, it is expected that strategies aimed at counteracting the negative immunoregulatory networks in the tumor microenvironment will develop into potent therapy for melanoma. Here, we report that programmed death-1high (PD-1high) tumor antigen (TA)-specific CD8+ T cells present at periphery and at tumor sites in patients with advanced melanoma upregulate IL-10 receptor (IL-10R) expression. IL-10 is produced by multiple PBMC subsets in melanoma patients and acts directly on IL-10R+ TA-specific CD8+ T cells to impede proliferation and increase apoptosis. PD-1 blockade augments IL-10R expression by TA-specific CD8+ T cells, suggesting that PD-1 blockade renders PD-1+ TA-specific CD8+ T cells more sensitive to the immunosuppressive effects of endogenous IL-10. As a result, we show that IL-10 blockade adds to PD-1 blockade to increase the expansion and functions of TA-specific CD8+ T cells. Collectively, our findings support dual IL-10 and PD-1 blockade to counteract melanoma-induced T cell dysfunction and enhance TA-specific CD8+ T cell responses in patients with advanced melanoma. Citation Format: Zhaojun Sun, Julien Fourcade, Ornella Pagliano, Joe-Marc Chauvin, Cindy Sander, John M. Kirkwood, Hassane M. Zarour. Interleukin-10 and programmed death-1 cooperate to regulate tumor antigen-specific CD8+ T cells in melanoma patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4046. doi:10.1158/1538-7445.AM2015-4046