title: Myeloid STAT3 Promotes Lung Tumorigenesis by Transforming Tumor Immunosurveillance into Tumor-Promoting Inflammation.
abstract: One of the most fundamental and challenging questions in the cancer field is how immunity in patients with cancer is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify the transcription factor STAT3 as the culprit responsible for this pathogenic event in lung cancer development. We found that antitumor type 1 CD4+T-helper (Th1) cells and CD8+T cells were directly counter balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8+T cells, enhancement of cytotoxicity toward CD4+and CD8+T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DC), and polarization of macrophages toward the M2 phenotype. The deletion of myeloid STAT3 boosted antitumor immunity and suppressed lung tumorigenesis. These findings increase our understanding of immune programming in lung tumorigenesis and provide a mechanistic basis for developing STAT3-based immunotherapy against this and other solid tumors.Cancer Immunol Res; 5(3); 257-68. ©2017 AACR.
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.|Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Jingjiao
authors.initials: J
authors.lastname: Zhou
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. xiaog2@upmc.edu quz@upmc.edu.|Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Qu
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.|Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Fan
authors.initials: F
authors.lastname: Sun
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.|Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.|Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Liwen
authors.initials: L
authors.lastname: Li
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Shapei
authors.initials: S
authors.lastname: Yan
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.|Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Laura P
authors.initials: LP
authors.lastname: Stabile
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Lin-Feng
authors.initials: LF
authors.lastname: Chen
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.|Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Siegfried
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. xiaog2@upmc.edu quz@upmc.edu.|Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Gutian
authors.initials: G
authors.lastname: Xiao
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000172:deficiency; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D006801:Humans; D007157:Immunologic Surveillance / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D008175:Lung Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism*; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; D050796:STAT3 Transcription Factor; D007371:Interferon-gamma