S. Li, Y. Bai, and X. Gao; Department of Radiation Oncology, Peking University First Hospital, Beijing, China
Purpose/Objective(s): Radiotherapy for massive tumors is a major problem in tumor radiotherapy today. Our research group found that partial stereotactic ablation (P-SABR) with local high-dose irradiation and whole low-dose irradiation has achieved ideal clinical results, but its specific mechanism is still unclear. In recent years, This study aimed to explore the immunological explanation of the therapeutic effect of P-SABR. Materials/
Methods: Using C57BL/6j mouse MC38 subcutaneous tumor model, the clinical treatment was simulated by giving P-SABR or SBRT. The tumor center was given 9Gy/f, 3 fractions, and the tumor periphery was given 3Gy/f, 6 fractions.The tumor growth curve and mouse survival curve were drawn to evaluate the similarity of animal experiments to clinical efficacy. We designed and made a new type of lead box to complete P-SABR on subcutaneous tumor of mice and protect normal tissues at the same time, and explored whether animal experiments can complete the central dose of P-SABR in dose distribution by using X-ray imaging film. The distribution of NETosis and CD8+T cells was explored by immunofluorescence of tumor specimen slices after radiotherapy. Whether P-SABR is CD8+T cell-dependent was explored by immune cell deletion experiment.we further investigated the in vivo distribution of 68Ga grazytracer in MC38 tumor–bearing mice pretreated with P-SABR. 68Ga-grazytracer uptake was highest 1 hour after injection. Results: P-SABR has similar curative effect to SBRT in animal model. P-SABR produced a large number of NETs in the tumor center, and CD8+T cells were distributed around the NETs. CD8+T cell deletion significantly reduced the efficacy of P-SABR, while NK cell or CD4+T cell deletion did not produce significant effects.P-SABR increaseed granzyme B levels during in tumor. Conclusion: In conclusion, animal experiments well restored the clinical efficacy of P-SABR. P-SABR produced a large number of NETs in tumor and hindered the infiltration of CD8+T cells. The therapeutic effect of P-SABR depends on the existence and activition of CD8+T cells.
