Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells

Ping Hsien Lee, Tori N. Yamamoto, Devikala Gurusamy, Madhusudhanan Sukumar, Zhiya Yu, Jane Hu-Li, Takeshi Kawabe, Arunakumar Gangaplara, Rigel J. Kishton, Amanda N. Henning, Suman K. Vodnala, Ronald N. Germain, William E. Paul, Nicholas P. Restifo

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2619-2634
Number of pages16
JournalJournal of Experimental Medicine
Volume216
Issue number11
DOIs
Publication statusPublished - 2019 Nov 1
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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