Blood monocytes and tumor-associated macrophages in human cancer: differences in activation levels

This study was performed to investigate functional properties of mononuclea r phagocytes isolated from ascitic fluid in patients with peritoneal carcin omatosis (PC), and potential immunomodulatory effects of soluble factors pr oduced or induced by human metastatic malignant cells. Phagocytic activity and nitric oxide production of peripheral blood monocytes (PBMo) and tumor- associated macrophages (TAM) or peritoneal macrophages (PEM) were synchrono usly examined in cancer patients and control individuals. Our results showe d that contrary to peripheral blood monocytes, where phagocytic activity wa s not altered, TAM had impaired phagocytic activity. Moreover, dilutions of crude supernatant from short-term cultures of the peritoneal cells obtaine d from ascitic fluid of patient with PC, cause a significant, dose dependen t inhibition of control PBMo and PEM phagocytosis, comparable to those in T AM, indicating that a soluble factor(s) plays a prominent role in this alte ration. Next, we investigated the potential of cancer patients mononuclear phagocytes to produce nitric oxide (NO). It was found that TAM produce four fold lower levels of NO than PEM from control subject, whereas monocytes pr oduce NO at levels comparable to those of corresponding controls. These dat a support the hypothesis that depressed TAM function may contribute to the mechanisms of tumor escape from immune destruction.