Modulation of anti-tumour immunity and the effect of bacterial endotoxin on the growth of different syngeneic tumours from small inocula in mice

Abstract

Studies were undertaken to determine the influence of E. coli lipopolysaccharide (LPS) on the growth of various doses of two antigenically-distinct syngeneic murine fibrosarcomas designated H1 and H7. The 'weakly' antigenic H1 tumour injected subcutaneously (s.c.) along the abdominal wall was profoundly susceptible to the growth-potentiating effects of a single intraperitoneal (i.p.) injection of 2 micrograms LPS, administered concurrently. 'Sneaking through' effects in control mice were observed with doses of 10 and 100 H1 tumour cells. Rejection of medium-sized inocula 25 or 500 H1 tumour cells were abolished by the administration of LPS. In contrast, the 'strongly' antigenic H7 tumour did not exhibit the 'sneaking through' phenomenon and its growth was only temporarily affected by LPS. Studies were also performed to determine the effect of LPS on the kinetics of delayed-type hypersensitivity (DTH) induced by mitomycin C-treated (MCT) H1 or H7 tumour cells inoculated s.c. into the footpads of mice. The 'strongly' antigenic MCT H7 tumour cells induced consecutive waves of footpad swelling of diminishing intensity and corresponded to periods of anti-tumour resistance. The specific phase of MCT H7-induced footpad swelling, maximal at day 6, was delayed in its induction if LPS was administered concurrently with MCT H7 tumour cells. In contrast, the 'weakly' antigenic MCT H1 tumour cells induced only one specific phase of footpad swelling which was rapidly down-regulated. The induction of immunity by MCT H1 tumour cells was also delayed by the concomitant administration of LPS. Because the 'weakly' antigenic H1 tumour was unable to sustain consecutive waves of anti-tumour immunity, the delay in the expression of such immunity by LPS allowed the H1 tumour cells to multiply to eventually overwhelm a rapidly down-regulated immune response. In contrast, the incidence of tumours arising from the 'strongly' antigenic H7 tumour cells was not significantly affected in LPS-treated mice because the tumour cells which escaped the first encounter with delayed anti-tumour immunity, succumbed to subsequent waves of resistance in both normal and LPS-treated mice injected with fewer than 1 X 10(5) H7 tumour cells.