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Data from Effector CD8+ T-cell Engraftment and Antitumor Immunity in Lymphodepleted Hosts Is IL7Rα Dependent

Authors :
Mark P. Rubinstein
David J. Cole
Shikhar Mehrotra
Elizabeth Garrett-Mayer
Kevin F. Staveley-O'Carroll
Guangfu Li
Stuart C. Gilreath
Bennett R. May
Brian P. Riesenberg
C. Bryce Johnson
Publication Year :
2023
Publisher :
American Association for Cancer Research (AACR), 2023.

Abstract

Adoptive cellular therapy, in which activated tumor-reactive T cells are transferred into lymphodepleted recipients, is a promising cancer treatment option. Activation of T cells decreases IL7 responsiveness; therefore, IL15 is generally considered the main driver of effector T-cell responses in this setting. However, we found in lymphodepleted mice that CD8+ T cells activated with IL12 showed enhanced engraftment that was initially dependent on host IL7, but not IL15. Mechanistically, enhanced IL7 responsiveness was conferred by elevated IL7Rα expression, which was critical for antitumor immunity. Elevated IL7Rα expression was achievable without IL12, as polyclonal CD8+ T cells activated with high T-cell receptor (TCR) stimulation depended on T-cell IL7Rα expression and host IL7 for maximal engraftment. Finally, IL12 conditioning during the activation of human CD8+ T cells, including TCR-modified T cells generated using a clinically relevant protocol, led to enhanced IL7Rα expression. Our results demonstrate the importance of the donor IL7Rα/host IL7 axis for effector CD8+ T-cell engraftment and suggest novel strategies to improve adoptive cellular therapy as a cancer treatment. Cancer Immunol Res; 3(12); 1364–74. ©2015 AACR.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........c2438f3e0154a753ac008da979de2c4d
Full Text :
https://doi.org/10.1158/2326-6066.c.6548579.v1