Presence of immunosuppressive factors in brain-tumor cyst fluid

The present investigation was conducted to examine the effects upon normal lymphocyte activation of the addition of brain-tumor cyst fluid or cerebrospinal fluid (CSF) to an in vitro culture system. It was believed that factors present in these fluids may play a role in local and systemic immunosuppression in brain-tumor patients. The authors evaluated the effect of the cyst fluid, CSF, and serum from eight patients with brain tumors (one astrocytoma, five glioblastoma multiforme, one medulloblastoma, and one microglioma) on mitogen-stimulated lymphocyte function as measured by 3H-thymidine incorporation, cell size distribution, and cellular proliferation. Lymphocytes from normal volunteers were incubated for 90 hours in culture medium with 10% pooled human serum, mitogens (phytohemagglutinin, concanavalin A, and pokeweed mitogen), and a range of volumes of cyst fluid or CSF from the tumor patients. Significant suppression of mitogen-induced activation of the lymphocytes was demonstrated in the presence of cyst fluid from five out of six patients, but the mitogen response was only minimally affected by the addition of the CSF from these patients to the culture medium. The suppression of lymphocyte activation by cyst fluid was directly proportional in several cases to the concentration of the cyst fluid. The total protein, albumin, and immunoglobulin (Ig) concentrations in the cyst fluids were observed to roughly correspond to the serum levels and were much higher than in CSF. These studies suggest that brain-tumor cells locally produce lymphocyte-suppressive factors which may then be released into blood. Preliminary characterization of the suppressive factor(s) responsible for the inhibition of lymphocyte function indicates that they are non-dialyzable and do not appear to be an IgG.