title: Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: correlation of CD163 expression, cytokine levels and early relapse.
abstract: Ovarian cancer is typically accompanied by the occurrence of malignant ascites containing large number of macrophages. It has been suggested that these tumor-associated macrophages (TAMs) are skewed to alternative polarization (M2) and thereby play an essential role in therapy resistance and metastatic spread. In our study, we have investigated the nature, regulation and clinical correlations of TAM polarization in serous ovarian cancer. Macrophage polarization markers on TAMs and ascites cytokine levels were analyzed for 30 patients and associated with relapse-free survival (RFS) in a prospective study with 20 evaluable patients. Surface expression of the M2 marker CD163 on TAMs was inversely associated with RFS (p < 0.01). However, global gene expression profiles determined for 17 of these patients revealed a mixed-polarization phenotype unrelated to the M1/M2 classification. CD163 surface expression also correlated with the ascites levels of IL-6 and IL-10 (p < 0.05), both cytokines induced CD163 expression, and their ascites levels showed a clear inverse association with RFS (p < 0.01). These findings define a subgroup of patients with high CD163 expression, high IL-6 and/or IL-10 levels and poor clinical outcome.
authors.affiliation: Clinic for Gynecology, Gynecological Oncology and Gynecological Endocrinology, Philipps University, Marburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Reinartz
authors.forename: Tim
authors.initials: T
authors.lastname: Schumann
authors.forename: Florian
authors.initials: F
authors.lastname: Finkernagel
authors.forename: Annika
authors.initials: A
authors.lastname: Wortmann
authors.forename: Julia M
authors.initials: JM
authors.lastname: Jansen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meissner
authors.forename: Michael
authors.initials: M
authors.lastname: Krause
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Schwörer
authors.forename: Uwe
authors.initials: U
authors.lastname: Wagner
authors.forename: Sabine
authors.initials: S
authors.lastname: Müller-Brüsselbach
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000276:immunology; D001201:Ascites / Q000276:immunology*; D016764:Cell Polarity; D018284:Cystadenocarcinoma, Serous / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000276:immunology; D059467:Transcriptome; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D016207:Cytokines; D011956:Receptors, Cell Surface
keywords: CD163; IL-10; IL-6; ovarian carcinoma; tumor-associated macrophages