PURPOSE: In this study, we hypothesized that systemic antitumor immunity might be enhanced by combining pulsed-wave ultrasound hyperthermia (pUSHT) with OK-432 and that the induced antitumor immunity could confer protection against tumorigenesis. These hypotheses were tested in bilateral and rechallenged tumor models. MATERIALS AND METHODS: Bilateral and rechallenged tumor models were applied in the studies. In the bilateral tumor model, BALB/c mice were inoculated with CT26-luc tumor cells into both flanks. The tumors in the right flank were treated with four courses of pUSHT with or without OK-432. In the rechallenged tumor model, tumor cells were implanted into the right flank. Once formed, the tumors were treated with pUSHT with OK-432, followed by surgical resection. New tumor cells were then implanted into the contralateral flank. The antitumor response was evaluated by infiltrated immune cells and the severity of necrosis/apoptosis in tumors. RESULTS: In the bilateral tumor model, the tumor growth rate and growth activity of both treated (100% reduction) and untreated tumors (90.5% reduction) were significantly inhibited with the combination treatment compared with the sham control group, and the systemic anti-tumor effect was prolonged. The survival rate was significantly enhanced (sham control: 8 days; OK+pUSHT: >20 days). IFNgamma(+) CD4 (treated tumor: 8.6-fold; untreated tumor: 4-fold), IFNgamma(+) CD8 (treated tumor: 6.7-fold; untreated tumor: 2.6-fold) T-cell and NK-cell (treated tumor: 4-fold; untreated tumor: 2.5-fold) infiltration were increased in the combination group compared with the control group. In the rechallenged tumor model, new tumors failed to form for the combination treatment. CONCLUSION: This experimental study combining pUSHT and OK-432 explored a new therapeutic strategy for controlling colon cancer metastasis, and the results showed that the combination treatment may produce an effective anti-tumor immune response.
Date:
2020-09-01
Relation:
International Journal of Radiation Oncology, Biology, Physics. 2020 Sep 1;108(1):140-149.
