The nonspecific immune suppression that occurs in cancer patients may enable otherwise immunogenic tumors to proliferate because of the absence of an effective anti-tumor host response. Suppressor lymphocytes have been implicated as the regulatory cells mediating this compromised immunological state, the molecular basis of which is not understood.
The specific aims of this research are to (1) test the hypothesis that certain tumors, bearing the oncofetal carcinoembryonic antigen (CEA), can elicit the release from suppressor lymphocytes of regulatory proteins which determine the immunosuppressed state, (2) to identify and characterize these suppressor lymphokines by their physiochemical and biological properties; (3) to elucidate the cellular interactions required for lymphokine release; and (4) to localize in vivo the lymphokine's site of action. Methods will include: purification of the CEA-induced suppressor factor by gel chromatography, preparative polyacrylamide gel electrophoresis, and isoelectric focusing; selective enrichment/depletion of mononuclear cell subpopulations to identify the cell type(s) responsible for suppressor factor release; microcytotoxicity assay using 51Cr-tumor cells to assess in vitro abrogation of three different anti-tumor immune responses by the supperessor lymphokine; development of a suppressor factor-specific monoclonal antibody in vivo immunocytochemical localization of the factor, and for extracting the suppressor factor from malignant ascites by affinity chromatography; and the construction of a highly quantitative and sensitive radioimmunoassay to measure CEA-induced suppressor factor in patients' body fluids and in tissue culture.
| Medoff, J R; Clack, V D; Roche, J K (1986) Characterization of an immunosuppressive factor from malignant ascites that resembles a factor induced in vitro by carcinoembryonic antigen. J Immunol 137:2057-64 |
