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

Yanxia Guo, Karina Pino-Lagos, Cory A. Ahonen, Kathy A. Bennett, Jinshan Wang, Joseph L. Napoli, Rune Blomhoff, Shanthini Sockanathan, Roshantha A. Chandraratna, Ethan Dmitrovsky, Mary Jo Turk, Randolph J. Noelle

Research output: Contribution to journalArticlepeer-review

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 a (dnRARa) 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.

Original languageEnglish (US)
Pages (from-to)5230-5239
Number of pages10
JournalCancer Research
Volume72
Issue number20
DOIs
StatePublished - Oct 15 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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