title: Distinct subpopulations of epithelial ovarian cancer cells can differentially induce macrophages and T regulatory cells toward a pro-tumor phenotype.
abstract: OBJECTIVE
  Presence of immune infiltrates in the tumor does not always correlate with an anti-tumoral immune response. We previously identified two subpopulations of epithelial ovarian cancer (EOC) cells with differential cytokine profile. We hypothesize that these two subpopulations of EOC cells may differentially regulate the immune phenotype in the tumor microenvironment and therefore affect the immune response.
  
  
  METHODS
  Macrophages derived from CD14+ monocytes and naive CD4+T cells were treated with conditioned media from two subpopulations of EOC cells. Differentiation markers and phagocytic activity were measured by western blot analysis and flow cytometry. Cytokine levels were quantified using xMAP technology.
  
  
  RESULTS
  Type I EOC cells are able to enhance macrophages' capacity for tumor repair and renewal by enhancing expression of scavenger receptors and by promoting the secretion of cytokines associated with tissue repair. On the other hand, type II EOC cells are able to create a tolerant microenvironment and prevent an immune response by inducing macrophages' to secrete IL-10 and by promoting the generation of T regs.
  
  
  CONCLUSIONS
  We demonstrate that each ovarian cancer cell subpopulation can induce a unique phenotype of macrophages and T cells, both associated with tumor-supportive function.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Ayesha B
authors.initials: AB
authors.lastname: Alvero
authors.forename: Michele K
authors.initials: MK
authors.lastname: Montagna
authors.forename: Vinicius
authors.initials: V
authors.lastname: Craveiro
authors.forename: Lanzhen
authors.initials: L
authors.lastname: Liu
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D002454:Cell Differentiation; D016207:Cytokines / Q000032:analysis; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D016207:Cytokines