Modification of cell cholesterol content of rat tumour cells. Effect upon their tumorigenicity and immunogenicity.

Abstract

Among the different constituents of the cell membrane, lipids have been poorly studied with respect to their role in the immunogenicity of tumour cells and their influence on the expression on tumour-associated antigens. Since liposome-associated antigens are more potent immunogens when the lipid matrix is in a rigid state, we have modified the lipid composition of rat hepatoma cells by incorporation of cholesteryl hemisuccinate (CH) into the lipid matrix, and studied its effect on the tumorigenicity and immunogenicity of these tumour cells in syngeneic animals. A slight and significant decrease of tumorigenicity of CH-enriched D23 cells was observed when 2×103 cells were injected SC, whereas with a higher tumour cell challenge there was no difference in the tumorigenicity of untreated or treated cells. The immunogenicity of CH-treated cells was tested by IP immunization with 107 or 106 cells followed 1 week later by an SC challenge with 2×104 viable D23 cells. No statistical difference was observed between the immunogenicity of CH-enriched cells and that of control cells on either tumour incidence or tumour growth rate. In addition, similar experiments performed with the spontaneous mammary carcinoma SP4 showed that CH-enriched SP4 cells were of lower immunogenicity and unable to induce a significant memory immunity. This lack of effect of the CH treatment on the immunogenicity was not related to the absence of incorporation of CH, since the CH treatment increased the cell lipid rigidity as determined by the increase of fluorescence anisotropy of the diphenyl hexatriene probe. These results obtained in two weak immunogenic tumour models underlined the need for further studies before such a lipid modification of cancer cells is applied in human immunotherapy trials.