Modification of the immunogenicity and antigenicity of rat hepatoma cells. II. Mild heat treatment.

I.p. immunization with gamma-irradiated hepatoma cells induces resistance to s.c. tumour-cell challenge in syngeneic WAB/Not rats. Mild heat treatment of these cells (greater than 41 degrees C for 30 min) destroyed this immunoprotective effect, but did not abolish tumour-specific antibody production in treated rats. The binding of syngeneic and alloantibodies to surface antigens expressed on hepatoma cells was unaffected by heat treatment. Thus, heat-treated gamma-irradiated hepatoma cells retain a serologically defined tumour-specific antigen but are unable to elicit immunoprotection. By examining the incorporation of radioactive precursors into DNA, RNA and protein in heat-treated cells, it was determined that above 41 degrees C there was a significant decrease in metabolic activity. It is postulated that for the effective induction of transplantation immunity to tumours, tumour-specific antigens should be present on the surface membranes of a metabolically active cell. This hypothesis accounts for the absence or marked reduction of immunoprotection induced by inviable or glutaraldehyde-treated cells, isolated cell membranes and soluble tumour extracts which retain serologically defined tumour-specific antigens.