Immunoregulatory factors (IRF) that suppress normal human peripherabl lood mononuclear cell (PBM) function can be extracted from a variety of fresh human tumors. Three molar potassium chloride extracts of 18 fresh human tumor specimens, including sarcomas, melanomas, and lung carcinomas, markedlyin hibited 3H-leucine and 3H-thymidine incorporation by PBM in response to mitogens (phytohemagglutinin, concanavalin A, Pokeweed mitogen) and pooled mitomycin C-treated allogeneic PBM. Induction of human allospecific cell-mediated cytotoxicity was also inhibited. Extracts of human normal and fetal tissues were not inhibitory. IRF could be extracted from either cultured tumor cells or from spent culture media from a melanoma cell line grown in chemically defined, serum-free media, demonstrating IRF is a tumor product. Although IRF were extracted from three histologically distinct tumors, the extracts had several common characteristics. Preincubation of PBM with IRF followed by washing prevented inhibition of lectin-stimulated proliferation. Inhibition was greatest when IRF were added immediateltyo cultures. IRF wereh eat-stable and resisted inactivation by papain, chymotrypsin, protease, and lipase; they could be partially inactivated by trypsin treatment. Inhibitory activity was removed from extracts by lentil lectin affinity chromatography and recovered by elution with 3% α-methyl-o-mannoside indicating the active moiety containeda carbohydrate. Inhibitory activity was also abolished by extremaec id or base conditions and treatment with 2-mercaptoethanol. These results demonstrate that factors produced by human tumors suppress a variety of cell-mediated immune responses. Factors from histologically different tumors possess similar biochemical and immunobiologic characteristics.
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Roth et al. (1982) studied this question.