title: Tumor-promoting effect of IL-23 in mammary cancer mediated by infiltration of M2 macrophages and neutrophils in tumor microenvironment.
abstract: Interleukin 23 (IL-23) is an inflammatory cytokine which plays a vital role in autoimmune diseases as well as in tumorigenesis. However, the role of IL-23 in tumor procession is still controversial and the underlying mechanism remains unclear. Here we established a stable cell line overexpressing IL-23 to prove that IL-23 promoted tumor growth and pulmonary metastasis through induction of tumor-related inflammation and absence of immune surveillance. IL-23 promotes tumor-associate inflammatory response such as infiltration of M2 macrophages, neutrophils and their elevated secretions of immunosuppressive cytokines transforming growth factor-β (TGF-β), IL-10 and vascular endothelial growth factor (VEGF) into tumor tissues, meanwhile the increase of the matrix metalloprotease MMP9. In addition, IL-23 increases the expression of the endothelial marker CD31 and proliferative marker Ki67 in tumors. Moreover, IL23 induces immunosuppression though reducing the infiltration of CD4+and CD8+T cells into tumor tissues. In conclusion, IL-23 is a considerable molecular in tumor progression, which simultaneously facilitates processes of pro-tumor inflammation, such as angiogenesis, immunosuppressive cytokines as well as infiltrations of M2 macrophages and neutrophils, and suppresses antitumor immune responses through reduction of CD4+T cells and CD8+T cells.
authors.affiliation: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People's Republic of China. Electronic address: wennie1228@126.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Nie
authors.affiliation: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Sang
authors.affiliation: Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People's Republic of China. Electronic address: xiangxianggao2008@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics* / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C556062:IL10 protein, mouse; D053759:Interleukin-23; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016753:Interleukin-10
keywords: IL-23; Inflammation; Macrophage; Mammary cancer; Neutrophil