Fig. 2. Sirpα^−/− macrophages confer complete responses after IR.

a–c Depletion of intratumoral macrophages diminished RT efficacy in Sirpα^−/− mice. MC38 tumor-bearing Sirpα^−/− mice were administered Cl2MDA-liposomes (Cl2MDP) or anti-CSF receptor antibodies (αCSF1R) to deplete macrophages starting 2 days prior to IR (8 Gy) (a). Depletion of intratumoral macrophages by Cl2MDP or αCSF1R was assessed by flow cytometry (b). Data from two independent experiments (3 mice/group in each experiment) are presented as mean ± SEM. n = 6 mice in each group. Tumor growth (c) in Sirpα^−/− mice was monitored after IR with or without macrophage depletion. Data from three independent experiments (3 mice/group in each experiment) are presented as mean ± SEM. n = 9 mice in each group. ***P < 0.001. d, f Combining adoptive infusion of Sirpα^−/− BMDMs with RT conferred tumor elimination in WT mice. As depicted in the therapeutic scheme (d), MC38 tumors in WT mice were treated once (1×) or twice (2×, 3-days interval) with intratumorally (i.t.) injected Sirpα^−/− or WT (Sirpα⁺) BMDMs (1 × 10⁴ per mm³ tumor mass) followed by IR (8 Gy). Tumor size (e) and mouse survival rate (f) were analyzed. Data from three independent experiments (3–4 mice/group in each experiment) are presented as mean ± SEM. n = 10 mice in each group. ***P < 0.001. g Percentage of transferred Sirpα^−/− BMDMs (GFP⁺) in total intratumoral macrophages 12 h after i.v. injection of Sirpα^−/− BMDMs (GFP⁺) (0.1–1 × 10⁷ per mouse). Data from three independent experiments (3 mice/group in each experiment) are presented as mean ± SEM. n = 9 mice in each group. h MC38 tumor growth in WT mice after 2× i.v. injection of BMDMs in combination with IR (8 Gy). Data from three independent experiments (3 mice/group) are presented as mean ± SEM. n = 9 mice in each group. ***P < 0.001. P values were calculated by one-way ANOVA with Tukey’s post hoc test (b, c, e, g) or one-way ANOVA with log-rank (Mantel–Cox) test (f). Source data are provided as a Source Data file.