The Temporal Effect of Low-Dose Irradiation on the Expression of SIRPa in Tumor-Associated Macrophages

Abstract

To investigate the effects of low-dose irradiation on the phagocytosis and phenotypic conversion of tumor-associated macrophages (TAMs) via the dynamic assessment of the expression of SIRPa. Experiments were performed with healthy male C57BL / 5J mice with subcutaneous inoculation of GFP-luc+ Lewis lung cancer cells in the back. The experimental group received treatment of 2Gy irradiation to the xenografted tumors on the 10th, 16th and 22nd days after the inoculation. The tumor response by volume measurement, the expression of SIRPa, phenotypes and phagocytic capacity of TAMs and spleen macrophages were evaluated or assayed using fluorescence-activated cell sorting (FACS) analysis on the 3rd, 6th and 9th day after irradiation. In comparison with the control group without irradiation, the radiation treatment significantly delayed the tumor growth. Radiotherapy significantly inhibited the expression of SIRPa on the surface of TAMs as well as splenic macrophages, while increasing amount of MHC II and enhanced phagocytic capability of TAMs on tumors cells were observed. The initial size of tumors (the interval between the treatment and inoculation) had impacts on the tumor growth delay amplitude, the expression of SIRPa and phagocytosis as a response to the irradiation. Better tumor control (volume reduction), lower SIRPa expression and improved phagocytosis were related to smaller treated tumors. Low-dose irradiation has the potential to promote the phenotype conversion of TAMs from pro-tumor M2 to anti-tumor M1 and restore the phagocytosis, which may be subject to tumor size.