title: IL-17A promotes immune cell recruitment in human esophageal cancers and the infiltrating dendritic cells represent a positive prognostic marker for patient survival.
abstract: We previously reported that tumor-infiltrating interleukin (IL)-17A-producing cells play a protective role in human esophageal squamous cell carcinoma (ESCC). However, the potential mechanisms involved remain unclear. In the present study, we investigated the effects of IL-17A on immune cell recruitment and function in ESCC. In vitro chemotaxis assays using the ESCC cell lines EC109 and KYSE30 demonstrated that although IL-17A showed no significant direct effects on the migration of T cells, natural killer (NK) cells as well as dendritic cells (DCs), it could induce ESCC tumor cells to produce inflammatory chemokines, for example, CXCL9, CXCL10 and CCL2, CCL20, which are associated with the migration of T cells, NK cells, and DCs, respectively. In addition, IL-17A enhanced the cytotoxic effects of NK cells against tumor cells by augmenting the expression of cytotoxic molecules, for example, tumor necrosis factor-α, interferon-γ, Perforin, and Granzyme B and activation receptors, for example, NKp46, NKp44, NTB-A, and NKG2D on NK cells. Furthermore, immunohistochemical analysis revealed that the density of IL-17A-producing cells was positively and significantly associated with the density of CD1a DCs in tumor tissues. With the analyses of 181 ESCC patients, we found a correlation of higher number of tumor-infiltrating CD1a DCs with significantly improved overall survival of patients with ESCC. This study provides further understanding of the roles of Th17 cells in ESCC, which may contribute to the development of novel cancer immunotherapy strategies.
authors.affiliation: *State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, P.R. China †Department of Surgery, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Ke
authors.initials: K
authors.lastname: Pan
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Zheng
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Li
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Qiu
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhao
authors.forename: De-Sheng
authors.initials: DS
authors.lastname: Weng
authors.forename: Qiu-Zhong
authors.initials: QZ
authors.lastname: Pan
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wang
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Jiang
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Chang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
authors.forename: Jian-Chuan
authors.initials: JC
authors.lastname: Xia
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000276:immunology* / Q000401:mortality; D045744:Cell Line, Tumor; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000276:immunology* / Q000401:mortality; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D018925:Chemokines; D018836:Inflammation Mediators; D020381:Interleukin-17