(P 281) FIVE DAY SPACING OF TWO FRACTIONATED ABLATIVE RADIOTHERAPIES ENHANCES ANTITUMOR IMMUNITY IN FIBROSARCOMA CELL LINE

Objective: This study aimed to enhance tumor control and abscopal effects by diverse stereotactic ablative body radiation (SABR) schedules.

Methods: FSaII (fibrosarcoma) cell was used for tumor growth delay assays after 1- or 5-day interval radiotherapy (RT) with 40 Gy. Immunodeficient BALB/c-nude, immunocompetent C3H mouse models were used. For immune monitoring, FSaII tumors were analyzed using flow cytometry, immunofluorescence staining, and qRT-PCR. The spleens were used for the ELISpot assay and flow cytometry to determine effector CD8 T-cells. Micrometastatic lung lesions were analyzed for the abscopal effect.

Results: Contrary to the high-dose 1-day interval RT, the 5-day interval RT significantly suppressed tumor growth in immunocompetent mice; this was not observed in immunodeficient mice. Five-day spacing was more effective than 1-day interval in enhancing the anti-tumor immunity via increasing the secretion of tumor-specific IFN-γ, activating the CD8 T-cells, and suppressing the monocytic myeloid-derived suppressor cells (M-MDSCs). The 5-day spacing inhibited lung micrometastases more effectively than did 1-day interval in FSaII.

Conclusion: Compared to the one-day interval RT, the five-day interval RT scheme demonstrated higher CD8 T-cell activity through M-MDSC inhibition. High levels of anti-tumor immunity resulted in high levels of tumor control indicating that FSaII tumors as a hot tumor could trigger a strong anti-tumor immune response. These results point to a novel therapeutic method for improving local clinical control during SABR: altering the time gap between fractions. In addition, FSaII tumors showed an abscopal influence on lung metastasis. To significantly boost an abscopal effect in various tumors, which are immunologically hot and cold, increased immune activation with ideal SABR fraction intervals would be required.