CARCINOEMBRYONIC ANTIGEN-INDUCED RELEASE OF A SUPPRESSOR FACTOR FROM NORMAL HUMAN-LYMPHOCYTES INVITRO

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (12) , 5822-5827
Abstract
Although it is generally accepted that tumor-bearing patients may be immunosuppressed, the mechanism for this effect is unclear. 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 was tested. Normal human peripheral blood mononuclear cells, after exposure to CEA for 48 h, 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 (0.2-100 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 MW was > 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 MW of 52,000, 77,000 and 171,000. Knowledge of immunomodulatory molecules present in cancer patients may suggest new modalities for therapy.