CURRENT RESEARCH REVIEW Defects in Monocyte Chemotaxis in Patients with Neoplastic Disease

The immuno-surveillance system is generally believed to detect and deter the spread of neoplastic disease. As major effecters of this complex system, infiltrating macrophages or monocytes accumulate at tumor sites and are thought to participate directly in tumor destruction [26, 381. Macrophage migration plays an essential role in such cell-mediated immune responses and in inflammatory reactions [65]. Studies of experimental tumor models have shown that macrophage migration is reduced in tumor-bearing animals [ 34, 41, 481. The migration of macrophages into sites of inflammation and macrophage accumulation around tumors are mediated primarily by soluble and surface-adherent chemical stimuli [40,60]. Soluble factors have been used for in vitro assays of directional locomotion, i.e., chemotaxis, to evaluate leukocyte function in tumor patients. Chemotaxis assays have employed primarily lymphokines (lymphocyte derived chemotactic factors) or complement fragments (C5a) as attractants for human monocytes [9, 44, 601. In addition, we have recently used a third group of chemoattractants, the synthetic formylpeptides, to study the migration of tumor patient neutrophils (PMN) and monocytes [68]. Chemotaxis of PMN from tumor patients is generally normal but a deficiency is clearly evident in the chemotaxis of monocytes from patients with malignant disease. In this review, we discuss the methodology used for leukocyte chemotaxis studies, summarize the data currently available on the chemotaxis of tumor patient leukocytes, and assess the biological and clinical significance of the leukotactic defect seen in these patients.