Variations in the level of haematogenous antitumour immunity during progressive tumour growth and spontaneous blood-borne metastatic spread.

Inbred DBA2 mice bearing the syngeneic 1699 mammary tumour in the hind limb were challenged intravenously with 125IUdR-labelled single 1699 cell suspensions, and the amount of radioactivity in the lungs compared 20--24 h later with that in the lungs of normal mice or in those of mice bearing the antigenically unrelated syngeneic SaD2 tumour. An immunologically specific decrease in radioactivity was evident at variable periods of time after tumour induction, depending on the number of cells used to induce the leg tumours, but fell below that in normal mice as the leg tumours progressed beyond a weight of approximately 1 g. As assessed by microscopic scanning of serial histological sections of the same lungs the incidence of spontaneous metastases rose to between 80 and 100% immediately the amount of cell loss from the lungs of the tumour-bearing mice reached that of the normal controls. This extremely rapid series of events does not allow a definitive conclusion as to whether immunity failed and led to metastatic spread or vice versa, but does underline the strong association of immunity with the blood-borne dissemination of tumour cells in this tumour system. Following excision of tumours, in no instance was immunity detected 14 days later, and in a single experiment did not reach detectable limits until 25 days after excision, at a time when the lung metastases were observed mostly to have regressed spontaneously.