The effects of dose and timing of anti-angiogenic therapy on intratumoral immune cells in its combination with radiotherapy

• 1、School of Radiation Medicine and Protection （SRMP） of Soochow University,su zhou 215123

Abstract：Radiation therapy is often combined with anti-angiogenic drugs, and it is not clear how different modes of administration of antiangiogenic drugs affect combination therapy. In this study, two orthotopic tumor models were used to analyze the effects of the dosage and administration time of Anlotinib on intratumoral immune cells in combination therapy. In 4T1 tumor model, increasing the dose of Anlotinib in combination decreased radiotherapy-induced T cell tumor infiltration and increased the proportions of Treg cells and PD1-expressing T cells. In EO771 tumor model, radiotherapy combined with low-dose Anlotinib increased the proportions of tintraumoral T cells, TAMs, and M-MDSCs (monocytic myeloid-derived suppressor cells), while increasing the combination dose of Anlotinib eliminated these effects. In addition, long-term Anlotinib combination therapy increased the proportions of intratumoral PMN-MDSC (polymorphonuclear myeloid-derived suppressor cells) in both models. These results suggest that radiotherapy in combination with higher doses of or longer-term anlotinib therapy is more likely to increase the immunosuppressive properties of the tumor microenvironment, which may compromise combination efficacy and induce drug resistance.

Keywords： Immunology Radiotherapy Anti-angiogenic therapy Myeloid-derived suppressor cells