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Host conditioning with IL-1β 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...

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Detalles Bibliográficos
Autores principales: Lee, Ping-Hsien, Yamamoto, Tori N., Gurusamy, Devikala, Sukumar, Madhusudhanan, Yu, Zhiya, Hu-Li, Jane, Kawabe, Takeshi, Gangaplara, Arunakumar, Kishton, Rigel J., Henning, Amanda N., Vodnala, Suman K., Germain, Ronald N., Paul, William E., Restifo, Nicholas P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829590/
https://www.ncbi.nlm.nih.gov/pubmed/31405895
http://dx.doi.org/10.1084/jem.20181218
Descripción
Sumario: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.