Exogenous IL-33 overcomes T cell tolerance in murine acute myeloid leukemia

Lei Qin, Donye Dominguez, Siqi Chen, Jie Fan, Alan Long, Minghui Zhang, Deyu Fang, Yi Zhang, Timothy M. Kuzel, Bin Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Emerging studies suggest that dominant peripheral tolerance is a major mechanism of immune escape in disseminated leukemia. Using an established murine acute myeloid leukemia (AML) model, we here show that systemic administration of recombinant IL-33 dramatically inhibits the leukemia growth and prolongs the survival of leukemia-bearing mice in a CD8+ T cell dependent manner. Exogenous IL-33 treatment enhanced anti-leukemia activity by increasing the expansion and IFN-γ production of leukemia-reactive CD8+ T cells. Moreover, IL-33 promoted dendritic cell (DC) maturation and activation in favor of its cross presentation ability to evoke a vigorous anti-leukemia immune response. Finally, we found that the combination of PD-1 blockade with IL-33 further prolonged the survival, with half of the mice achieving complete regression. Our data establish a role of exogenous IL-33 in reversing T cell tolerance, and suggest its potential clinical implication into leukemia immunotherapy.

Original languageEnglish (US)
Pages (from-to)61069-61080
Number of pages12
JournalOncotarget
Volume7
Issue number38
DOIs
StatePublished - 2016

Keywords

  • AML
  • CD8 T cells
  • IL-33
  • ST2
  • Tolerance

ASJC Scopus subject areas

  • Oncology

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