IMMUNOSUPPRESSIVE PLASMA FACTORS IN MALIGNANT DISEASE

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Abstract
Naturally occurring substances in plasma capable of suppressing immune responses have been described in health and in benign and malignant diseases. The present study attempted to identify the factors responsible for the immunosuppressive activity of plasma from healthy subjects (n = 5) and patients with benign (10) and malignant (12) diseases. Plasma samples were fractionated by gel filtration and the distribution of specific protein was determined. The suppressive activity of plasma and plasma fractions against autologous and allogenic lymphocytes was measured using a rapid in vitro electrophoretic test. Plasma suppressive activity (PSA) was low in normal subjects and well nourished patients with benign disease and was associated entirely with alpha-2-macroglobulin (a2M). PSA was significantly increased in patients with malignancy and was associated mainly with a2M although immune complexes, IgG and small molecular weight substances were also immunosuppressive. Plasma a2M concentrations were similar in all groups but the suppressive activity associated with a2M differed dramatically. The study demonstrates that PSA can be measured quantitatively and that a2M is an important immunoregulatory protein in cancer patients. On the basis of the results obtained a new hypothesis of tumour-mediated immune suppression is proposed.

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