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J Exp Med. 2019 Aug 12. pii: jem.20181218. doi: 10.1084/jem.20181218. [Epub ahead of print]

Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells.

Author information

1
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD leepinghsien@gmail.com.
2
Center for Cell-Based Therapy, National Cancer Institute, National Institutes of Health, Bethesda, MD.
3
Cytokine Biology Unit, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
4
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
5
Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA.
6
Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
7
Cellular Immunology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
8
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD drnickrestifo@gmail.com.

Abstract

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.

PMID:
31405895
DOI:
10.1084/jem.20181218

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