1. Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells
- Author
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Rigel J. Kishton, Arunakumar Gangaplara, Madhusudhanan Sukumar, William E. Paul, Tori N. Yamamoto, Ronald N. Germain, Amanda N. Henning, Ping-Hsien Lee, Devikala Gurusamy, Zhiya Yu, Suman K. Vodnala, Jane Hu-Li, Nicholas P. Restifo, and Takeshi Kawabe
- Subjects
0301 basic medicine ,Adoptive cell transfer ,T-Lymphocytes ,medicine.medical_treatment ,T cell ,Interleukin-1beta ,Immunology ,Melanoma, Experimental ,Mice, Transgenic ,Inflammation ,Biology ,Lymphocyte Activation ,Immunotherapy, Adoptive ,Article ,03 medical and health sciences ,0302 clinical medicine ,Aldesleukin ,Cell Line, Tumor ,medicine ,Animals ,Immunology and Allergy ,Research Articles ,Mice, Knockout ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,fungi ,Immunotherapy ,Adoptive Transfer ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Interleukin 15 ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Cytokines ,medicine.symptom ,Homing (hematopoietic) - Abstract
Lee et al. reveal that administration of IL-1β can alter the host environment to augment the magnitude and functionality of CD8+ T cells, thereby improving the efficacy of adoptively transferred tumor-reactive T cells in treating large, established tumors in mice., 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.
- Published
- 2019
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