Modulation of anti-tumour immunity induced by syngeneic mitomycin C-treated murine tumour cells

Abstract

Experiments were performed to examine the kinetics of delayed-type hypersensitivity (DTH) to mitomycin-C-treated syngeneic murine fibrosarcomas inoculated into the footpads of mice. Evidence is presented to show that a "strongly" antigenic tumour, designated H7, elicits consecutive waves of footpad swelling in both primary and secondary responses. Periods of anti-tumour resistance coincided with the expression of each successive wave of footpad swelling in normal and immune mice. The down-regulation of the response, between the successive peaks of footpad swelling, was accompanied by active tumour growth. In contrast, the non-cross-reacting "weakly" antigenic tumour, designated H1, induced footpad swelling which was expressed only once after either primary or secondary sensitization. Unlike that induced by the "strongly" antigenic H7 tumour, the anti-tumour immunity to the H1 tumour was not sustained beyond its initial specific phase. Consequently, H1 tumour cells which survived the initial phase of anti-tumour immunity appeared to encounter no further resistance. Thus the distinctive feature of the "weakly" antigenic H1 tumour was its inability to sustain consecutive waves of tumour resistance as exhibited by the "strongly" antigenic H7 tumour. It is proposed that "weakly" and "strongly" antigenic tumours are distinguished by their different abilities to down-regulate the anti-tumour immune response. The "weakly" antigenic tumour induces specific immunity which is rapidly down-regulated while that induced by the "strongly" antigenic tumour is sustained by successive waves of anti-tumour activity of diminishing intensity. Suppression of some but not all waves of footpad swelling occurred in mice with growing H7 tumours.