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Title: Immunological studies on whole-body hyperthermia treatment for advanced cancer
Author: Gee, Adrian Philip
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1978
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There is renewed interest in the use of induced hyperthermia in the treatment of malignant disease. It has been proposed that the anti-tumour effects of hyperthermia are mediated by the immune system. The aim of this investigation was to determine whether whole-body hyperthermia (41.8°C) affected the immune status of patients with advanced cancer. General immunocompetence has been monitored before, during, and after therapy, using several tests, in vitro. During treatment there was a stress-mediated leucocytosis, characterised by an increase in the concentration of phagocytically active immature neutrophils, a T-lymphopenia, and a B-lymphocytosis, but no change in the total lymphocyte concentration. Lymphoid antibody-dependent cellular cytotoxicity, and phytohaema ggWgt induced lymphocyte transformation, were slightly depressed by heating. The day following treatment, the T lymphocyte concentration remained depressed, and there was a fall in the level of serum complement. Within 3-5 days of treatment, most parameters had returned to their pre-treatment values, and there was a marked increase in the T lymphocyte response to PHA, to 2-3 times the prehyperthermia level. This was no longer evident within a week of treatment. Hyperthermia therapy had no significant long-term effect on any of the indices of cellular, or humoral, immunocompetence that were monitored. Heating lymphocyte suspensions in vitro, for 2h at 42°C, abolished PHA-induced RNA and DNA synthesis, and severely depressed their capacity to form spontaneous normal and 'rapid' rosettes with unsensitised sheep erythrocytes. The ability of lymphoid cells to lose antibody-coated tumour cells was also reduced by heating the effector population in vitro. Granulocytes heated at 42°C were less efficient at phagocytosing low concentrations of latex particles. The depression of lymphocyte immune function occurred, to a lesser extent, when whole blood was heated in vitro before separation of the lymphocytes. These results indicate that heat treatment, both in vivo and in vitro, depresses general immunocompetence. In the clinical situation the depression lasts 24-48h following treatment, during which, thermoresistant, viable tumour cells may be seeded into the peripheral circulation, and become established as metastases.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available