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Defective Antitumor Function of Monocyte-Derived Macrophages from Epithelial Ovarian Cancer Patients

Authors' Affiliations: ¹ The University of Texas Graduate School of Biomedical Sciences and ² Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Ralph Freedman, Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Unit 1362, P.O. Box 301439, Houston, TX 77230-1439. Phone: 713-792-2764; Fax: 713-792-7586; E-mail: rfreedma{at}mdanderson.org.

Purpose: Monocytes/macrophages (MO/MA) are an important but heterogeneous population of immune inflammatory cells that have diverse effector functions. We examined and compared these differences in peripheral blood and ascites of epithelial ovarian cancer patients with peripheral blood of normal donors.

Experimental Design: Comparisons were made of cell surface subsets, cytokine production, and FcR-dependent cytotoxicity of CD14⁺ MO/MA and the CD14^brightCD16^–HLA-DR⁺ MO/MA subset in normal donor peripheral blood and peripheral blood and ascites from epithelial ovarian cancer patients. Studies were done on monocyte-derived macrophages cultured with macrophage colony-stimulating factor and activated with lipopolysaccharide or a combination of lipopolysaccharide plus recombinant IFN-.

Results: We determined that MO/MA or its subset from epithelial ovarian cancer patients had altered morphology and significantly less antibody-dependent cell-mediated cytotoxicity and phagocytic activity than did MO/MA from normal donors. Our findings also showed that monocyte-derived macrophages from both epithelial ovarian cancer patients and normal donors produce macrophage colony-stimulating factor–stimulated cytokines, including interleukin-8, tumor necrosis factor-, and interleukin-6.

Conclusions: These findings highlight for the first time the defective antibody-dependent cell-mediated cytotoxicity and phagocyte functions of epithelial ovarian cancer–associated MO/MA, which could have implications for immunobiotherapeutic strategies.

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