Abstract IA15: Role of PD-1 and LAG-3 in cancer immunotherapy.

Abstract

Abstract PD-1 and LAG-3 are negative regulatory molecules expressed on the cell surface of “exhausted” or non-functional CD8 T cells in both cancer and in infectious disease. In several cancer models, blocking both molecules shows a synergistic anti-tumor effect, without overt signs of autoimmunity. In more recent studies, we have examined the role of LAG-3 and/or PD-1 blockade on memory induction in vivo. Interestingly, we found that a short course (1 week) of combined antibody blockade results in a significant increase in the frequency of memory T cells over 30 weeks later. Augmented CD8 T cell responses were not apparent in the secondary lymphoid organs, but rather manifested as an increase in tissue resident responses. Responding cells in the combined blockade group also showed an increase in polyfunctional cytokine production, confirming the potential for increased effector function. Taken together, these data support our previous studies implying that simultaneous blockade of multiple immune checkpoints may be required for optimal anti-tumor immunity. Citation Format: Charles G. Drake. Role of PD-1 and LAG-3 in cancer immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA15.