While studies have implicated a role of vitamin A (VA) in host resistance to infectious disease, little is known as to the role of VA and its active metabolite, retinoic acid (RA) in host defense against cancer. Herein, it is shown for the first time that local RA production within the tumor microenvironment (TME) is increased up to 5-fold compared to naïve surrounding tissue, with a commensurate increase in RA signaling to regionally infiltrating tumor-reactive T cells. Conditional disruption of RA signaling in CD8+ T cells using a dominant negative Retinoic Acid Receptor α (dnRARα) illustrated that RA signaling is required for tumor-specific CD8+ T cell expansion/accumulation and protective anti-tumor immunity. Specific deletion of RARα, RARβ and RARγ in CD8+ T cells further demonstrated that RARα is required for CD8+ T cell survival, whereas RARβ is indispensable for bacteria-specific CD8+ T cell expansion in response to bacterial infection. These studies established a novel function of RA essential for both anti-tumor and infection CD8+ T cell immunity.
- Copyright © 2013 by The American Association of Immunologists, Inc.