Fig. 1

Treatment outcomes after therapy with NBTXR3, high- and low-dose radiotherapy, and immunotherapy. A Treatment schema for NBTXR3 given with high-dose and low-dose radiotherapy. Mice were subcutaneously inoculated with 5 × 10⁴ 344SQR cells in the right legs on day 0 (to establish primary tumors) and in the left legs on day 3 (to establish secondary tumors). NBTXR3 was delivered to the primary tumor by intratumoral injection on day 6. Primary tumors were treated with three 12-Gy fractions on day 7, 8, and 9 (HDXRT). Secondary tumors were irradiated with two 1-Gy fractions on day 12 and 13 (LDXRT). Anti-PD1 (200 μg) and anti-CTLA4 (100 μg) were given by intraperitoneal injection on days 4, 7, 10, and 13, and anti-PD1 treatment was continued once a week from day 20 until day 62. B Changes in primary tumor volumes over time. C Changes in secondary tumor volumes over time. Data are shown as means for each treatment group (n  = 7 or 8), with bars indicating standard error of the mean. D Survival rates and median survival times for each treatment group. E Number of spontaneous lung metastases on day 16 in each treatment group. All of the mice were injected with both anti-PD1 and anti-CTLA4, and all mice were euthanized when the any tumor exceeded 14 mm in diameter. F Individual primary tumor volumes for each treatment group. G Individual secondary tumor volumes for each treatment group. Data are expressed as means  ±  standard error of the mean (SEM). P  < 0.05 was considered statistically significant. *P  < 0.05, **P  < 0.01, ***P  < 0.001, ****P  < 0.0001, NS not significant. HDXRT high-dose radiotherapy; LDXRT low-dose radiotherapy; ICIs immune checkpoint inhibitors