Immunosuppressive effect of acute-phase reactant proteins in vitro and its relevance to cancer

Acute-phase reactant proteins reach abnormally high levels in patients with cancer, and correlate with the extent of disease. In this study, several acute-phase glycoproteins, and serum albumin as a control, were tested at different concentrations for their ability to modify the blastogenic response of lymphocytes from 30 normal donors to PHA and the chemotactic response of monocytes from 15 normal donors to casein. In high concentrations approximating those found in cancer patients, but not in normal concentrations, haptoglobin and fibrinogen inhibited both functions to different degrees. Orosomucoid inhibited only monocyte chemotaxis, while ceruloplasmin and alpha 1-antitrypsin affected neither function. Increasing concentrations of PHA did not overcome the blocking effect of haptoglobin and fibrinogen on blastogenesis, suggesting that PHA-protein interaction was not responsible for the effect observed. The three proteins that did not suppress blastogenesis individually did so strongly when combined. It is suggested that these glycoproteins, synthesized by the liver in response to an inflammatory stimulus, may act as 'non-specific blocking factors' protecting tumors against the host's immunological attack. This non-specific blocking activity of the acute-phase proteins may contribute to the 'immune escape' of the tumor.