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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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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 |
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author | 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. |
author_facet | 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. |
author_sort | Lee, Ping-Hsien |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6829590 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68295902019-11-06 Host conditioning with IL-1β 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. J Exp Med Research Articles 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. Rockefeller University Press 2019-11-04 2019-08-12 /pmc/articles/PMC6829590/ /pubmed/31405895 http://dx.doi.org/10.1084/jem.20181218 Text en This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles 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. Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells |
title | Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells |
title_full | Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells |
title_fullStr | Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells |
title_full_unstemmed | Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells |
title_short | Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells |
title_sort | host conditioning with il-1β improves the antitumor function of adoptively transferred t cells |
topic | Research Articles |
url | 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 |
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