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Host conditioning with IL-1ß improves the antitumor function of adoptively transferred T cells.
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.
Afiliación
  • Lee PH; Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD leepinghsien@gmail.com.
  • Yamamoto TN; Center for Cell-Based Therapy, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Gurusamy D; Cytokine Biology Unit, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
  • Sukumar M; Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Yu Z; Center for Cell-Based Therapy, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Hu-Li J; Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA.
  • Kawabe T; Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Gangaplara A; Center for Cell-Based Therapy, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Kishton RJ; Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Henning AN; Center for Cell-Based Therapy, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Vodnala SK; Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Germain RN; Center for Cell-Based Therapy, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Paul WE; Cytokine Biology Unit, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
  • Restifo NP; Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
J Exp Med ; 216(11): 2619-2634, 2019 11 04.
Article en En | MEDLINE | ID: mdl-31405895
Host conditioning has emerged as an important component of effective adoptive cell transfer-based immunotherapy for cancer. High levels of IL-1ß are induced by host conditioning, but its impact on the antitumor function of T cells remains unclear. We found that the administration of IL-1ß increased the population size and functionality of adoptively transferred T cells within the tumor. Most importantly, IL-1ß 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-1ß-stimulated host cells. In addition, IL-1ß 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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Melanoma Experimental / Activación de Linfocitos / Linfocitos T / Inmunoterapia Adoptiva / Interleucina-1beta Límite: Animals Idioma: En Revista: J Exp Med Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Melanoma Experimental / Activación de Linfocitos / Linfocitos T / Inmunoterapia Adoptiva / Interleucina-1beta Límite: Animals Idioma: En Revista: J Exp Med Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos