TY - JOUR
T1 - Restored Thymic Output after Androgen Blockade Participates in Antitumor Immunity
AU - Polesso, Fanny
AU - Caruso, Breanna
AU - Hammond, Scott A.
AU - Moran, Amy E.
N1 - Publisher Copyright:
Copyright © 2023 by The American Association of Immunologists, Inc.
PY - 2023/2/15
Y1 - 2023/2/15
N2 - The thymus is a hormone-sensitive organ, which involutes with age in response to production of sex steroids. Thymic involution leads to a decrease in the generation of recent thymic emigrants (RTEs), resulting in a reduced response to immune challenges such as cancer. Interestingly, the standard of care for prostate cancer patients is androgen deprivation therapy (ADT), which leads to thymic regeneration and an increase in thymic output. It remains unknown whether these newly produced T cells can contribute to the antitumor immune response. This study defines the kinetics of thymic regeneration in response to ADT in mice, determining that thymic epithelial cell proliferation is critical for the increase in RTE output. Using a mouse model to track RTE in vivo, we demonstrate that these newly generated RTEs can traffic to tumors, where they become activated and produce effector cytokines at levels similar to more mature T cells. Collectively, these data suggest that RTEs produced from ADT-induced thymic regeneration could be harnessed for the antitumor immune response.
AB - The thymus is a hormone-sensitive organ, which involutes with age in response to production of sex steroids. Thymic involution leads to a decrease in the generation of recent thymic emigrants (RTEs), resulting in a reduced response to immune challenges such as cancer. Interestingly, the standard of care for prostate cancer patients is androgen deprivation therapy (ADT), which leads to thymic regeneration and an increase in thymic output. It remains unknown whether these newly produced T cells can contribute to the antitumor immune response. This study defines the kinetics of thymic regeneration in response to ADT in mice, determining that thymic epithelial cell proliferation is critical for the increase in RTE output. Using a mouse model to track RTE in vivo, we demonstrate that these newly generated RTEs can traffic to tumors, where they become activated and produce effector cytokines at levels similar to more mature T cells. Collectively, these data suggest that RTEs produced from ADT-induced thymic regeneration could be harnessed for the antitumor immune response.
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U2 - 10.4049/jimmunol.2200696
DO - 10.4049/jimmunol.2200696
M3 - Article
C2 - 36548468
AN - SCOPUS:85147318016
SN - 0022-1767
VL - 210
SP - 496
EP - 503
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -