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Title: Naturally occurring immunosuppressive substances in plasma, with special reference to malignant disease
Author: Francis, David Michael Andrew
ISNI:       0000 0001 3481 6567
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1988
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Evidence suggests that host immunity has an important bearing on the growth and spread of malignant tumours. Naturally occurring immuno? suppressive substances have been demonstrated in the plasma of cancer patients, but the nature and relevance of such factors to the impaired immunity of cancer patients and to tumour behaviour are poorly understood. Cellular immunity is impaired in malnourished subjects also; although nutritional repletion with fat-free intravenous fluids may improve nutritional and immunological parameters, the immunological consequences of using solutions rich in polyunsaturated fatty acids are largely unknown. The aims of the study were to quantify the lymphocyte suppressive activity of plasma (plasma suppressive activity, PSA) and to identify specific substances associated with suppressive activity in plasma from normal subjects, and patients with benign or malignant diseases and with various degrees of malnutrition. Also, an attempt was made to correlate PSA with tumour behaviour in an animal model, firstly by measuring PSA before, during and after tumour growth, and secondly by observing tumour growth after artificially increasing PSA. In other studies in vitro lymphocyte reactivity was measured firstly after incubation with fat emulsion, and secondly in patients receiving parenteral fat emulsions. The study found that PSA was low in healthy subjects and patients with benign disease, and was associated entirely with the plasma protease inhibitor alpha-2-macroglobulin (A2M). PSA was raised moderately, although significantly, in malnourished patients with benign disease and correlated significantly with the extent of nutritional impairment; PSA was associated mainly with A2M but also with a small molecular weight peptide fraction. Patients with malignant disease had very high PSA which did not correlate with nutritional impairment and which was associated mainly with A2M but also with immune complexes, IgG, Fc fragments and a small molecular weight peptide fraction. Plasma A2M concentrations did not differ significantly between subject groups although the amount of suppressive activity associated with A2M did. PSA increased with tumour growth in the animal model but returned to pre-tumour levels after complete removal of tumours. Tumour growth was increased significantly in animals in which PSA was elevated at the time of tumour transplantation. Intravenous fluids containing fat significantly depressed in vitro lymphocyte reactivity in the laboratory and clinical studies. The study shows that A2M is an important regulator of lymphocyte reactivity in health and in malignant disease, and demonstrates a mechanism of immunological evasion by tumours by way of naturally occurring immunoregulatory plasma factors.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Immune response to cancer][Cancer