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A retinoic acid--rich tumor microenvironment provides clonal survival cues for tumor-specific CD8(+) T cells.


ABSTRACT: 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 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 ? (dnRAR?) 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.

SUBMITTER: Guo Y 

PROVIDER: S-EPMC3766319 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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A retinoic acid--rich tumor microenvironment provides clonal survival cues for tumor-specific CD8(+) T cells.

Guo Yanxia Y   Pino-Lagos Karina K   Ahonen Cory A CA   Bennett Kathy A KA   Wang Jinshan J   Napoli Joseph L JL   Blomhoff Rune R   Sockanathan Shanthini S   Chandraratna Roshantha A RA   Dmitrovsky Ethan E   Turk Mary Jo MJ   Noelle Randolph J RJ  

Cancer research 20120817 20


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 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 cell  ...[more]

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