TY - JOUR
T1 - Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells
AU - Lee, Ping Hsien
AU - Yamamoto, Tori N.
AU - Gurusamy, Devikala
AU - Sukumar, Madhusudhanan
AU - Yu, Zhiya
AU - Hu-Li, Jane
AU - Kawabe, Takeshi
AU - Gangaplara, Arunakumar
AU - Kishton, Rigel J.
AU - Henning, Amanda N.
AU - Vodnala, Suman K.
AU - Germain, Ronald N.
AU - Paul, William E.
AU - Restifo, Nicholas P.
N1 - Funding Information:
The research was supported by the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases and National Cancer Institute, National Institutes of Health, and by the Cancer Moonshot program for the Center for Cell-Based Therapy at the National Cancer Institute, National Institutes of Health. The work was also supported by the Mil-stein Family Foundation. This work used the computational resources of the National Institutes of Health High Performing Computation Biowulf cluster (http://hpc.nih.gov).
Publisher Copyright:
© 2019 Rockefeller University Press. All rights reserved.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Host conditioning has emerged as an important component of effective adoptive cell transfer-based immunotherapy for cancer. High levels of IL-1β are induced by host conditioning, but its impact on the antitumor function of T cells remains unclear. We found that the administration of IL-1β increased the population size and functionality of adoptively transferred T cells within the tumor. Most importantly, IL-1β enhanced the ability of tumor-specific T cells to trigger the regression of large, established B16 melanoma tumors in mice. Mechanistically, we showed that the increase in T cell numbers was associated with superior tissue homing and survival abilities and was largely mediated by IL-1β-stimulated host cells. In addition, IL- 1β enhanced T cell functionality indirectly via its actions on radio-resistant host cells in an IL-2- and IL-15-dependent manner. Our findings not only underscore the potential of provoking inflammation to enhance antitumor immunity but also uncover novel host regulations of T cell responses.
AB - Host conditioning has emerged as an important component of effective adoptive cell transfer-based immunotherapy for cancer. High levels of IL-1β are induced by host conditioning, but its impact on the antitumor function of T cells remains unclear. We found that the administration of IL-1β increased the population size and functionality of adoptively transferred T cells within the tumor. Most importantly, IL-1β enhanced the ability of tumor-specific T cells to trigger the regression of large, established B16 melanoma tumors in mice. Mechanistically, we showed that the increase in T cell numbers was associated with superior tissue homing and survival abilities and was largely mediated by IL-1β-stimulated host cells. In addition, IL- 1β enhanced T cell functionality indirectly via its actions on radio-resistant host cells in an IL-2- and IL-15-dependent manner. Our findings not only underscore the potential of provoking inflammation to enhance antitumor immunity but also uncover novel host regulations of T cell responses.
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U2 - 10.1084/jem.20181218
DO - 10.1084/jem.20181218
M3 - Article
C2 - 31405895
AN - SCOPUS:85074554041
SN - 0022-1007
VL - 216
SP - 2619
EP - 2634
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 11
ER -
