Journal
ONCOTARGET
Volume 7, Issue 38, Pages 61069-61080Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11179
Keywords
IL-33; ST2; tolerance; AML; CDS T cells
Categories
Funding
- National Institutes of Health [CA149669]
- Northwestern University RHLCCC Flow Cytometry Facility, a Cancer Center Support Grant [NCI CA060553]
- Walter S. and Lucienne Driskill Immunotherapy Research fund
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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 11-33 treatment enhanced anti-leukemia activity by increasing the expansion and IFN-gamma 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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