Immunosuppressive factors in serum of patients with gastric carcinoma

Sera from patients with gastric carcinoma markedly suppressed the normal lymphocyte response to phytohemagglutinin (PHA) when compared with normal sera. The effect of this inhibition was well correlated with the degree of advance of the disease. Fractionation of normal and cancerous sera was carried out by DEAE-cellulose column chromatography using a continuous concave gradient. The elution patterns of the two kinds of sera were quite similar and separated into nine fractions. Protein analysis by immunoelectrophoresis and immunodiffusion showed no difference in subfractions between normal and cancerous sera. However, inhibitory activities of cancerous sera on PHA response of normal lymphocytes were found in alpha-globulin, beta-globulin, and alpha2-macroglobulin fractions. On the other hand, in the fractions from normal serum, alpha- and beta-globulin fractions showed a similar degree of inhibition to PHA response of normal lymphocytes, but alpha2-macroglobulin fraction had no inhibitory activity. Such inhibitory fractions showed an immunosuppressive activity not only to PHA response of normal lymphocytes in vitro, but also due to the induction of splenic plaque-forming cells in vivo. The electrofocusing patterns of alpha2-macroglobulin fractions obtained from normal and cancerous sera showed a remarkable difference in protein composition. These results indicated that the function of lymphocytes may be regulated by a variety of humoral factors and, especially in patients with gastric carcinoma, the cell-mediated immunity may be modified by some factors not present in normal serum.