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

Abstract

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.

Influence of Surgery on the Responsiveness of Blood Lymphocytes in Patients With Advanced Cancer

“…Moreover, Miller and Baker [29] and Werkmeister et al [30] did not find any correlation between the proliferative responses of lymphocytes to ConA and PHA and SC activity in either cancer patients or controls. In contrast, in patients with advanced cancer of the head, neck, and colon, Hubbard et al [31] observed a diminished ConA-SC activity compared to healthy controls, which correlated with a lower responsiveness to PHA and C o d . Uchida et al [32] observed that the ConA-induced SC activity in pleural effusions, but not in peripheral blood, was effected partially by nonspecific suppressor cells which appeared to be T cells, and which were able to third postoperative day in the nonadvanced group.…”

Overview of immunology of oral squamous cell carcinoma

“…It is evident that humoral factors may suppress cell-mediated immune responses, and various suppressors of leukocytes may regulate cell-mediated immune responses in patients with head and neck cancer. [ 48 ]…”