Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 216, Issue 11, Pages 2619-2634Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20181218
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Funding
- Milstein Family Foundation
- Intramural Research Programs of the National Institute of Allergy and Infectious Diseases
- Cancer Moonshot program for the Center for Cell-Based Therapy at the National Cancer Institute, National Institutes of Health
- National Cancer Institute, National Institutes of Health
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Host conditioning has emerged as an important component of effective adoptive cell transfer-based immunotherapy for cancer. High levels of IL-1 beta are induced by host conditioning, but its impact on the antitumor function of T cells remains unclear. We found that the administration of IL-1 beta increased the population size and functionality of adoptively transferred T cells within the tumor. Most importantly, IL-1 beta 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-1 beta-stimulated host cells. In addition, IL1 beta 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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