Abstract 3528: Anti-CD47 immunotherapy regulates T cell metabolism and hypoxia in the tumor microenvironment

Dysfunction of infiltrating CD8+ effector T cells can be induced by hypoxia and aberrant tumor metabolite uptake in the microenvironment causing an “exhausted” T cell phenotype that limits anti-tumor immunosurveilance. Hence- therapeutic strategies aimed at improving T cell bioenergetics have the potential to reinvigorate T cell responses to reduce tumor burden. CD47 is a widely expressed receptor that controls phagocytic activity by engaging its counter receptor, SIRPα, in macrophages. Also autonomously or by binding to its ligand Thrombospondin-1 CD47 activation can control cell fate under stress. Our prior work shows that targeting CD47 on CD8+ T cells enhanced cytotoxicity against cancer cells. Moreover, depletion of CD8+ T cells in murine models reversed the anti-tumor effect of anti-CD47 therapy. Our new data shows that targeting CD47 reduced the growth of B16 melanoma tumors by approximately 50% (1607 ± 213.7, saline vs. 815.1 ± 67.8, CD47 (-) *p Citation Format: Yismelin R. Feliz-Mosquea, Elizabeth Stirling, Katherine L. Cook, Adam Wilson, Manish Bharadwaj, Anthony J. Molina, Liliya Yamaleyeva, Pierre L. Triozzi, David R. Soto-Pantoja. Anti-CD47 immunotherapy regulates T cell metabolism and hypoxia in the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3528.