Carcinoembryonic antigen-induced release of a suppressor factor from normal human lymphocytes in vitro

Although it is generally accepted that tumor-bearing patients may be immunosuppressed, the mechanism for this effect is unclear. Therefore, we tested the hypothesis that a tumor-associated macromolecule, carcinoembryonic antigen (CEA), could itself suppress lymphocyte function, as quantitated by uptake of [3H]thymidine by lymphocytes stimulated with the plant lectin, phytohemagglutinin. Normal human peripheral blood mononuclear cells, after exposure to CEA for 48 hr, subsequently released a factor in vitro which markedly inhibited phytohemagglutinin-stimulated lymphocytes. In further experiments, this factor release was confirmed to be initiated by CEA and not by a contaminant, and to be induced over a broad range of CEA concentrations (0.2 to 100 ng/ml). Suppression could not be accounted for by factor-associated cytotoxicity toward indicator cells, nor was it secondary to a mixed-lymphocyte reaction, nor could CEA alone (without factor) modulate proliferation. In studies to characterize the factor, its molecular weight was greater than 10,000, its activity was partially denatured by heat and proteases, and the isoelectric point was 3.4. Polyacrylamide gel electrophoresis of an "active" fraction revealed protein bands with molecular weights of 52,000, 77,000, and 171,000. Knowledge of immunomodulatory molecules present in cancer patients may suggest new modalities for therapy.