Inhibition of growth and metastasis of syngeneic transplantable tumours by an aromatic retinoic acid analogue

Summary An aromatic retinoic acid analogue (Ro 10-9359) previously shown to be capable of inhibiting the growth and metastasis of immunogenic sarcomas and carcinomas (see accompanying paper) was tested for its anti-tumour effects in various categories of immune-deprived mice. Non-specific immunosuppression evoked by sub-lethal whole-body X-irradiation abolished the inhibition of tumour growth induced by Ro 10-9359 in immunocompetent syngeneic hosts. Also, retinoid treatment of three categories of T-lymphocyte-deprived mice (nu/nu; thymectomized-irradiated; and cyclosporin A-treated) was ineffective in reducing the local growth rate or inhibiting spontaneous metastasis of their tumours; in fact, regardless of retinoid treatment the tumours grew faster and metastasized more widely in immunosuppressed animals than in controls. Silica and carrageenan (which are toxic to monouclear phagocytes) did not interfere with the inhibitory effects of Ro 10-9359 on tumour growth, and did not themselves potentiate metastasis; however, both agents prevented the abolition of DM6 carcinoma metastasis by retinoids. APD, which inhibits the accessory cell function of macrophages did not reduce the effectiveness of Ro 10-9359 against local tumours. However, in contrast to silica and carrageenan this agent did increase the incidence of metastasis of DM6 carcinoma from 40% to 60%, but in the presence of retinoids only 20% of mice succumbed to secondary disease. These results suggest an essential role for T lymphocytes in retinoid-induced local tumour growth inhibition, and a further contribution of mononuclear phagocytes to the prevention of metastatic disease.