Host conditioning with IL-1{beta} improves the antitumor function of adoptively transferred T cells
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.
Source: The Journal of Experimental Medicine - Category: Internal Medicine Authors: Lee, P.-H., Yamamoto, T. N., Gurusamy, D., Sukumar, M., Yu, Z., Hu-Li, J., Kawabe, T., Gangaplara, A., Kishton, R. J., Henning, A. N., Vodnala, S. K., Germain, R. N., Paul, W. E., Restifo, N. P. Tags: Innate Immunity and Inflammation, Tumor Immunology Articles Source Type: research
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