In vitro studies of cell-mediated immunity in cancer

Abstract

A review of the literature on cell-mediated immunity to cancer revealed that many in vitro techniques have been used to investigate this subject. The techniques had been introduced to detect reactions between lymphocytes and tumour antigens, and serum factors which modify these reactions. Most of the methods were applicable to both animals and man and clinical uses in human cancer have been suggested, but the many disadvantages of existing methods seem to make them unsuitable for routine use.The leucocyte adherence inhibition (LAI) test was introduced as an improved technique in tumour immunology, and the original work of this thesis is concerned with the development, investigation and application of this techniqueAnti-tumour immunoreactivity to methylcholanthrene-induced tumours in mice was studied and specific cell-mediated immunity was demonstrated. Murine tumours showed individual tumour specificity. The LAI test was shown to depend on the production of a soluble factor which had characteristics in common with known lymphokines. It was produced by T-lymphocytes and its action was directed against adherent cells in the leucocyte-antigen mixtures. An indirect or 2-stage LAI test which depended on the presence of a soluble mediator was developed and this technique was used to study the kinetics of cell-mediated immunity in mice after tumour transplantation.Specific blocking of lymphocyte-antigen interaction was demonstrated in the serum of tumour-bearers and the kinetics of blocking in mice before and after tumour removal were investigated. Serum from mice after tumour removal was found to contain unblocking factors which interfered with the action of blocking factors in tumour-bearer serum.The LAI test was used to study immunoreactivity in human cancer. Four types of tumours were used: melanoma, colorectal carcinoma, medullary carcinoma of the thyroid and hepatoma. Patients were studied for reactivity to tumour antigens before and after tumour removal.The specificity of the LAI reaction with human tumours was related to the histological type of tumour rather than individual tumours. In hepatoma the situation was more complex and the LAI test was used to analyse the antigens involved. Serum blocking factors were detected consistently in patients with progressing tumours.The LAI test correlated well with the presence of tumour in both animals and man, and was shown to be a useful diagnostic aid in human cancer.