Monocyte function in patients with bronchogenic carcinoma

Depressed immune function is often observed in patients with carcinoma, but the cellular basis for this defect has not been elucidated. The authors are investigating two functions of the peripheral blood monocyte(MN) that are related to its role in the immune response: immunoprotein receptor activity and chemotaxis. MN were separated from venous blood by Ficoll Hypaque gradient centrifigation. Chemotaxis of mixed mononuclear cells under agarose was carried out by the method of Nelson et. al. (J. Immun. 115:1650,1975) using zymosan activated serum as the chemoattractant. Monocytes attached to glass coverslips in the Leighton tubes were incubated with sheep erythrocytes coated with dilutions of 7S rabbit anti Forssman antibody (EA) or 19S antibody and complement (EAC) and were scored for rosette formation and phagocytosis. There was at least a 15% lower chemotactic index (chemotactic movement: random movement ratio) in 4 of 5 patients studied when compared with normal controls (mean difference: 22%). Random migration of MN was greater than control in 3 of 5 patients. Incubation of MN for four hours with 100 micrograms/ml Levamisole(L), an immunostimulatory agent recently demonstrated to enhance chemotaxis and receptor activity of normal MN (Schmidt and Douglas, submitted) resulted in an 18% increase in the chemotactic index in the patient group. Assays of MN immunoprotein receptors revealed one patient with significantly lower binding of both EA and EAC while the other patient monocytes demonstrated normal receptor activity (4/5). Incubation of patients' MN monolayers with L (100 micrograms/ml) for 4 hours resulted in increases in the percentage of MN ingesting EA at an antibody dilution of 1:6400 comparable to that observed in normals. These studies suggest that evaluation of monocyte receptors and function in vitro and their pharmacologic modulation may offer an approach to characterization of immunologic abnormalities in cancer.