Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: Correlation of CD163 expression, cytokine levels and early relapse

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. What's new? The peritoneal environment plays a critical role in the spread of ovarian cancer, ultimately becoming a malignant ascites, rich in tumor-associated macrophages (TAMs), in advanced stages of disease. TAMs in this context have been implicated in therapy resistance and metastatic spread, though their function remains unclear. Here, TAMs from malignant ascites in patients with serous ovarian carcinoma were found to express a mixed-polarization phenotype and highly variable levels of the surface marker CD163. Elevated CD163 was associated with early disease relapse and increased IL-6 and IL-10 levels. Further investigation of these changes in surface marker expression could provide insight into mechanisms of progression in ovarian cancer.