Defective suppressor cell activity in cancer patients: a defect in immune regulation

Although suppressor cells appear to be involved in the normal regulatory mechanism of the lymphoid system, they are also considered to have a role in the immunosuppression of certain malignancies. Suppressor activity of lymphocytes can be reproducibly measured by use of the mixed lymphocyte culture-mitogen interaction (MLC-M) in which the stimulating cell either is in the basal state or has been induced by Concanavalin A. This yields a quantitative measure of resting suppressor cell activity as well as the maximum generation of suppressor activity as induced by Con A. This test was performed, using autologous and allogenic cell combinations in a group of 13 cancer patients and 18 normal controls. Normal lymphocytes activated by Con A in 48-hour lymphocyte cultures significantly decreased the mitogenic response of lymphocytes from healthy, male donors to phytohemagglutinin (PHA), Con A, and Pokeweed mitogen (PWM) in both autologous and homologous systems. In contrast, Con A activated lymphocytes from cancer patients demonstrated diminished suppressor activity compared with controls in autologous (P less than 0.01), and allogenic (P less than 0.005) systems. There was a correlation between the degree of immunosuppression and suppressor cell activation: i.e., the patients most depressed generally had the lowest suppressor cell activation. Untreated lymphocytes from cancer patients also exerted suppressive effects on normal lymphocyte responses, suggesting an increased resting level of suppressor cells. These data suggest that in addition to having depressed cellular immune responses, cancer patients frequently have reduced capability to generate suppressor cell activity, which implies a generalized defect in this aspect of immune regulation.