Enhancement of tumor antigen expression and inhibition of pulmonary metastasis of rat fibrosarcoma cells by local radiotherapy.

Pulmonary metastasis formation after local radiotherapy against a rat fibrosarcoma was investigated. KMT-l7 fibrosarcoma cells were transplanted into the hind leg in syngeneic WKA rats and two different doses (30Gy, 60Gy) of irradiation from a 60 Co source were applied 5 days after transplantation. Pulmonary metastasis was inhibited by 30Gy irradiation rather than 60Gy irradiation, which was enough to almost completely cure the local tumors. This inhibitory effect of 30Gy irradiation was induced by the continued presence of irradiated tumors. As for pulmonary metastasis, the different effects of irradiation doses were not recognized when the tumor was removed surgically I day after irradiation, but when it was removed 4 days after 30Gy irradiation significantly inhibited metastasis. Expression of tumor-associated antigen (TAA), termed CE7 antigen, on the cell surface was enhanced effectively and continuously by 30Gy irradiation rather than by 60Gy. With this increase in CE7-expressing cells, the enhancement of anti-tumor immunity of spleen cells was observed in an in vitro 125 I-ludR release assay and an in vivo tumor-neutralizing assay (Winn assay). The above results suggest that an appropriate dose of irradiation such as 30Gy, to a local tumor can efficiently enhance the TAA expression and that TAA-expressing cells may stimulate anti-tumor immunity resulting in inhibition of pulmonary metastasis. This phenomenon may offer the possibility of resistance to micrometastasis through the induction of antitumor effector cells.