A Retinoic Acid-Rich Tumor Microenvironment Provides Clonal Survival Cues for Tumor-Specific CD8(+) T Cells

作者：Guo Yanxia; Pino Lagos Karina; Ahonen Cory A; Bennett Kathy A; Wang Jinshan; Napoli Joseph L; Blomhoff Rune; Sockanathan Shanthini; Chandraratna Roshantha A; Dmitrovsky Ethan; Turk Mary Jo; Noelle Randolph J^*

来源：Cancer Research, 2012, 72(20): 5230-5239.

DOI：10.1158/0008-5472.CAN-12-1727

While vitamin A has been implicated in host resistance to infectious disease, little is known about the role of vitamin A and its active metabolite, retinoic acid (RA) in host defenses against cancer. Here, we show that local RA production within the tumor microenvironment (TME) is increased up to 5-fold as compared with naive 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 alpha (dnRAR alpha) established that RA signaling is required for tumor-specific CD8(+) T-cell expansion/accumulation and protective antitumor immunity. In vivo analysis of antigen-specific CD8(+) T-cell responses revealed that early T-cell expansion was RA-independent; however, late T-cell expansion and clonal accumulation was suppressed strongly in the absence of RA signaling. Our findings indicate that RA function is essential for the survival of tumor-reactive CD8(+) T cells within the TME. Cancer Res; 72(20); 5230-9.

• 出版日期2012-10-15