title: Host miR155 promotes tumor growth through a myeloid-derived suppressor cell-dependent mechanism.
abstract: miR155 is a regulator of immune cell development and function that is generally thought to be immunostimulatory. However, we report here that genetic ablation of miR155 renders mice resistant to chemical carcinogenesis and the growth of several transplanted tumors, suggesting that miR155 functions in immunosuppression and tumor promotion. Host miR155 deficiency promoted overall antitumor immunity despite the finding of defective responses of miR155-deficient dendritic cells and antitumor T cells. Further analysis of immune cell compartments revealed that miR155 regulated the accumulation of functional myeloid-derived suppressive cells (MDSC) in the tumor microenvironment. Specifically, miR155 mediated MDSC suppressor activity through at least two mechanisms, including SOCS1 repression and a reduced ability to license the generation of CD4(+)Foxp3(+) regulatory T cells. Importantly, we demonstrated that miR155 expression was required for MDSC to facilitate tumor growth. Thus, our results revealed a contextual function for miR155 in antitumor immunity, with a role in MDSC support that appears to dominate in tumor-bearing hosts. Overall, the balance of these cellular effects appears to be a root determinant of whether miR155 promotes or inhibits tumor growth.
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Siqi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Cancer Therapy and Research Center, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Cong
authors.initials: C
authors.lastname: Ye
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Donye
authors.initials: D
authors.lastname: Dominguez
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cancer Therapy and Research Center, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Curiel
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Deyu
authors.initials: D
authors.lastname: Fang
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Kuzel
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. bin.zhang@northwestern.edu.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology*; D022423:Myeloid Cells / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D059016:Tumor Microenvironment
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D001119:Arginase