title: Immunosuppressive effect of renal cell carcinoma on phenotype and function of dendritic cells.
abstract: Dendritic cells (DCs) play an important role in anti-renal cell carcinoma (RCC) immunity. The aim of the study was to investigate effect of mimic RCC microenvironment on phenotype and function of DCs. We isolated conditioned media (CM) from supernatants of culturing RCC cells and adjacent non-RCC cells in patients. CD14+ monocytes were obtained from healthy donors. The monocytes derived DCs were treated by RCC CM and non-RCC CM. Maturation markers CD80, CD83, CD86, and HLA-DR on DCs were analyzed using flow cytometry, while the levels of IL-10, TGF-β, and IL12p70 in supernatants were examined by ELISA. The DCs migration treated with RCC CM and non-RCC CM was investigated using transwell assay. The DCs treated and allogenic T cells were co-cultured for detecting T-cell proliferation and change of phenotype on the T cells. Our results indicated that RCC CM inhibited the up-regulation of CD80,CD83, CD86, and HLA-DR in response to LPS in treated DCs and increased IL-10 and TGF-β secretion but reduced IL12p70 production. Moreover, the migration ability of DCs treated with RCC CM was also inhibited, compared to DCs treated with adjacent non-RCC CM. In addition, T-cell proliferation was suppressed in co-culture assay with DCs treated with RCC CM; proportion CD25+Foxp3+ regulatory T cells were induced to increase. This study suggests that RCC CM can inhibit maturation of DCs and impair its function; moreover, DCs treated with RCC CM induce regulatory T cells increase, thus could contribute RCC escape from antitumor immunity.
authors.affiliation: Department of Urology, Cancer Hospital, Harbin Medical University, No.150 Haping Road, Harbin City, 150086, Heilongjiang Province, China, tenglichen@2008.sina.com.
authors.forename: Lichen
authors.initials: L
authors.lastname: Teng
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chen
authors.forename: Dexin
authors.initials: D
authors.lastname: Ding
authors.forename: Hongshuang
authors.initials: H
authors.lastname: Dai
authors.forename: Guobin
authors.initials: G
authors.lastname: Liu
authors.forename: Changfu
authors.initials: C
authors.lastname: Li
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D003713:Dendritic Cells / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000032:analysis; D016753:Interleukin-10 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment; D015854:Up-Regulation / Q000187:drug effects; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D017077:Culture Media, Conditioned; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D016753:Interleukin-10; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; D000097802:CD83 Antigen