title: Exogenous IL-33 overcomes T cell tolerance in murine acute myeloid leukemia.
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.
authors: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.|Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Lei
authors: L
authors: Qin
authors: Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Donye
authors: D
authors: Dominguez
authors: Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Siqi
authors: S
authors: Chen
authors: Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Jie
authors: J
authors: Fan
authors: Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Alan
authors: A
authors: Long
authors: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.|Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Minghui
authors: M
authors: Zhang
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Deyu
authors: D
authors: Fang
authors: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors: Yi
authors: Y
authors: Zhang
authors: Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Timothy M
authors: TM
authors: Kuzel
authors: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.|Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Bin
authors: B
authors: Zhang
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003713:Dendritic Cells / Q000378:metabolism; D007108:Immune Tolerance; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000378:metabolism*; D000067596:Interleukin-33 / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000627:therapeutic use; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011994:Recombinant Proteins; D007371:Interferon-gamma
keywords: AML; CD8+ T cells; IL-33; ST2; tolerance