Extended Data Fig. 10: T-cell independent abscopal effects upon radiation therapy and CD47 blockade in cancer models.
From: Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect
a. Human Ramos lymphoma cells were engrafted into both flanks of NSG immunodeficient mice and only right-side tumors were irradiated. b. Growth curves of Ramos xenografts. N = 1 experiment with n = 6 mice. Irradiated tumors: **p = 0.0022, **p = 0.0047, non-irradiated tumors: **p = 0.0021, ***p = 0.0002. c. MC38 allografts in C57Bl/6 mice were treated with the indicated treatments (as in Fig. 7a,b) and tumor-infiltrating macrophages (F4/80 + CD11b+), CD206 + M2-like macrophages, CD4+ T cells and CD8 + T cells were quantified by immunostaining. N = 1 experiment with n = 6 tumors. CD11b + F4/80+: ***p = 0.0001, ***p = 0.0001, CD206+: *p = 0.0158, CD4+: **p = 0.057, *p = 0.0110. d. Proposed model for macrophage-mediated abscopal effects. Irradiation of tumors results in the secretion of inflammatory molecules such as CSF1 and other cytokines that can activate macrophages. Blockade of CD47 further activate the migratory and phagocytic activity of macrophages. CD47 blockade is critical at both the irradiated and non-irradiated tumor sites but not required systemically. Activated macrophages can migrate from the irradiated site to the non-irradiated site, and possibly also directly from the circulation. Not shown in the model, T cells can cooperate with macrophages to enhance antitumor responses. Two-tailed t-tests following two-way ANOVA were performed in (b) (irradiated tumors: p < 0.0001, non-irradiated tumors: p < 0.0001). Two-tailed t-tests following one-way ANOVA were performed in (c) (CD11b + F4/80+: p < 0.0001, CD206+: p = 0.0121, CD4+: p = 0.0217, CD8+: p = 0.4010) Error bars represent SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
