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*
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.
https://doi.org/10.1158/0008-5472.CAN-12-1727
Myeloid cells
In-vivo
Improves
10.1158/0008-5472.CAN-12-1727
Dive into the research topics of 'A retinoic acid-rich tumor microenvironment provides clonal survival cues for tumor-specific CD8+ T cells'. Together they form a unique fingerprint.
Tumor Microenvironment Medicine & Life Sciences 100%
Tretinoin Medicine & Life Sciences 98%
Cues Medicine & Life Sciences 83%
T-Lymphocytes Medicine & Life Sciences 59%
Vitamin A Medicine & Life Sciences 25%
CD8 Antigens Medicine & Life Sciences 16%
Retinoic Acid Receptors Medicine & Life Sciences 15%
Guo, Y., Pino-Lagos, K., Ahonen, C. A., Bennett, K. A., Wang, J., Napoli, J. L., Blomhoff, R., Sockanathan, S., Chandraratna, R. A., Dmitrovsky, E., Turk, M. J., & Noelle, R. J. (2012). A retinoic acid-rich tumor microenvironment provides clonal survival cues for tumor-specific CD8+ T cells. Cancer Research, 72(20), 5230-5239. https://doi.org/10.1158/0008-5472.CAN-12-1727
Guo, Yanxia ; Pino-Lagos, Karina ; Ahonen, Cory A. et al. / A retinoic acid-rich tumor microenvironment provides clonal survival cues for tumor-specific CD8+ T cells. In: Cancer Research. 2012 ; Vol. 72, No. 20. pp. 5230-5239.
@article{bab5ada1edbf469cbfd4b7e061be7067,
title = "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 na{\"i}ve 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.",
keywords = "Dendritic cells, Myeloid cells, In-vivo, Differentiation, Expression, Generation, Immunity, Receptor, Induction, Improves",
author = "Yanxia Guo and Karina Pino-Lagos and Ahonen, {Cory A.} and Bennett, {Kathy A.} and Jinshan Wang and Napoli, {Joseph L.} and Rune Blomhoff and Shanthini Sockanathan and Chandraratna, {Roshantha A.} and Ethan Dmitrovsky and Turk, {Mary Jo} and Noelle, {Randolph J.}",
doi = "10.1158/0008-5472.CAN-12-1727",
journal = "Cancer Research",
publisher = "American Association for Cancer Research Inc.",
Guo, Y, Pino-Lagos, K, Ahonen, CA, Bennett, KA, Wang, J, Napoli, JL, Blomhoff, R, Sockanathan, S, Chandraratna, RA, Dmitrovsky, E, Turk, MJ & Noelle, RJ 2012, 'A retinoic acid-rich tumor microenvironment provides clonal survival cues for tumor-specific CD8+ T cells', Cancer Research, vol. 72, no. 20, pp. 5230-5239. https://doi.org/10.1158/0008-5472.CAN-12-1727
A retinoic acid-rich tumor microenvironment provides clonal survival cues for tumor-specific CD8+ T cells. / Guo, Yanxia; Pino-Lagos, Karina; Ahonen, Cory A. et al.
In: Cancer Research, Vol. 72, No. 20, 15.10.2012, p. 5230-5239.
T1 - A retinoic acid-rich tumor microenvironment provides clonal survival cues for tumor-specific CD8+ T cells
AU - Guo, Yanxia
AU - Pino-Lagos, Karina
AU - Ahonen, Cory A.
AU - Bennett, Kathy A.
AU - Wang, Jinshan
AU - Napoli, Joseph L.
AU - Blomhoff, Rune
AU - Sockanathan, Shanthini
AU - Chandraratna, Roshantha A.
AU - Dmitrovsky, Ethan
AU - Turk, Mary Jo
AU - Noelle, Randolph J.
N2 - 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.
AB - 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.
KW - Dendritic cells
KW - Myeloid cells
KW - In-vivo
KW - Differentiation
KW - Expression
KW - Generation
KW - Immunity
KW - Receptor
KW - Induction
KW - Improves
U2 - 10.1158/0008-5472.CAN-12-1727
DO - 10.1158/0008-5472.CAN-12-1727
JO - Cancer Research
JF - Cancer Research
Guo Y, Pino-Lagos K, Ahonen CA, Bennett KA, Wang J, Napoli JL et al. A retinoic acid-rich tumor microenvironment provides clonal survival cues for tumor-specific CD8+ T cells. Cancer Research. 2012 Oct 15;72(20):5230-5239. doi: 10.1158/0008-5472.CAN-12-1727