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

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

22 Citas (Scopus)

Resumen

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.
Idioma originalInglés estadounidense
Páginas (desde-hasta)5230-5239
Número de páginas10
PublicaciónCancer Research
Volumen72
N.º20
DOI
EstadoPublicada - 15 oct 2012
Publicado de forma externa

Huella Profundice en los temas de investigación de 'A retinoic acid-rich tumor microenvironment provides clonal survival cues for tumor-specific CD8<sup>+</sup> T cells'. En conjunto forman una huella única.

Citar esto