Abstract LB-144: Deletion of Map4k4 enhances CD8 T cell function

Map4k4 is broadly expressed across different cell types and its function is cell type and context dependent. Although it is expressed in multiple types of immune cells, its specific function in different subsets of lymphocytes and myeloid cells have yet to be determined. Here we demonstrate that reducing MAP4K4 activity can enhance CD8 T cell functions in the context of anti-tumor and anti-viral responses. Inducible deletion of Map4k4 increases CD8 T cell activation, proliferation, cytokine production, and target cell killing in vitro, and enhances CD8 T cell-mediated suppression of tumor growth as well as antigen-specific response to viral infection in vivo. Intratumoral T cells showed evidence of enhanced activation and produced more inflammatory cytokines when stimulated ex vivo. Simultaneously reducing MAP4K4 activity and blocking PDL1 resulted in additive anti-tumor efficacy. Our data suggests that MAP4K4 could be a potential target to augment anti-tumor and immunity. Citation Format: Emel Esen, Weilan Ye, Rajiv Jesudason, Ismail Sergin. Deletion of Map4k4 enhances CD8 T cell function [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-144.