Oncotarget

Research Papers:

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 and Bin Zhang _

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Oncotarget. 2016; 7:61069-61080. https://doi.org/10.18632/oncotarget.11179

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Abstract

Lei Qin1,2, Donye Dominguez2, Siqi Chen2, Jie Fan2, Alan Long2, Minghui Zhang1,2, Deyu Fang3, Yi Zhang1, Timothy M. Kuzel2, Bin Zhang1,2

1Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China

2Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

3Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

Correspondence to:

Bin Zhang, email: [email protected]

Keywords: IL-33, ST2, tolerance, AML, CD8+ T cells

Received: February 11, 2016     Accepted: July 27, 2016     Published: August 10, 2016

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.


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