title: Hypoxia-induced CCL28 promotes recruitment of regulatory T cells and tumor growth in liver cancer.
abstract: Tumor cells craft microenvironment to overcome growth disadvantages and adjust to escape the immunosurveillance during tumorigenesis and metastasis. The evolving adaption to the changing microenvironment is exemplified by the development of strategies to deal with hypoxia resulted from fast proliferation of the tumor cells. In this study, we found that hypoxia hepatocellular carcinoma (HCC) cells recruited Regulatory T cells (Tregs) and expressed more Chemokine (C-C motif) ligand 28 (CCL28). Deletion of CCL28 inhibited Treg recruitment. Furthermore, overexpression of CCL28 promoted tumor growth and Treg infiltration in vivo. Enhanced angiogenesis and VEGF expression was also observed. Moreover, inhibition of HIF1α reversed hypoxia-induced CCL28 upregulation. Taken together, our results demonstrate that HCC recruits Tregs to promote angiogenesis under hypoxic condition by upregulating CCL28 expression. These findings establish a link between Tregs and hypoxia in HCC growth and may provide a new potential therapeutic target for treating HCC.
authors.affiliation: Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, P.R. China.|Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Medical Sciences, Tianjin Medical University, Tianjin, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Medical Sciences, Tianjin Medical University, Tianjin, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Medical Sciences, Tianjin Medical University, Tianjin, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Medical Sciences, Tianjin Medical University, Tianjin, P.R. China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Medical Sciences, Tianjin Medical University, Tianjin, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Lu
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Medical Sciences, Tianjin Medical University, Tianjin, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000276:immunology*; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D064593:Heterografts; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008113:Liver Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating; D051379:Mice; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D047368:Tumor Burden; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: C414047:CCL28 protein, human; D019742:Chemokines, CC; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: CCL28; HCC; HIF1α; Treg; angiogenesis