Fig. 4: RANKL pharmacological inhibition reinforces anti-CTLA4 and anti-PD-L1 anti-tumor response in RANK+/+ but not in RANK−/− tumors. | Nature Communications

Fig. 4: RANKL pharmacological inhibition reinforces anti-CTLA4 and anti-PD-L1 anti-tumor response in RANK+/+ but not in RANK−/− tumors.

From: Inhibition of RANK signaling in breast cancer induces an anti-tumor immune response orchestrated by CD8+ T cells

Fig. 4

a Graphs showing the percentage of PD-1+ cells within CD11b− lymphocytes (n = 12 RANK+/+ tumors, n = 10 RANK−/− tumors; PD-1+ within CD11b−CD45+; ****p < 0.0001), CTLA4 within CD4+ T cells (n = 8; CTLA4 within CD3+ CD8−CD11b−CD45+; *p = 0.0166), PD-L1 within tumor CD45− cells (n = 26 RANK+/+ tumors, n = 22 RANK−/− tumors; *p = 0.017), and Tregs (n = 12 RANK+/+ tumors, n = 10 RANK−/− tumors; FoxP3+ CD25+ CD4+ CD11b− within CD45+; ****p < 0.0001) in RANK+/+ and RANK−/− transplants in syngeneic C57BL/6 mice. Each dot represents an individual tumor transplant derived from two to five different primary tumors. Mean, SEM, and t-test two-tailed p-values are shown (*p < 0.05; ****p < 0.0001). b Experimental scheme for early treatments with anti-RANKL (a-RL), anti-CTLA4, anti-PD-L1, or their respective isotype controls (rat IgG2A and mouse IgG2b). All treatments were administered i.p, two times/week, and started 3 days after injection of RANK+/+ and RANK−/− tumor cells into the mammary gland of syngeneic C57BL/6 mice. c, d Tumor growth curves for early treatments (scheduled as in Fig. 4b) of RANK+/+ (c) and RANK−/− (d) tumor cells injected in syngeneic C57BL/6. Each thin curve represents one single tumor. Each thick curve represents the mean of all the tumors that received the specific treatment. Linear regression analysis was performed and a two-tailed p-value was calculated to compare the tumor growth slopes after the specified treatments (****p < 0.0001). e Experimental scheme for late treatments with anti-RL, anti-CTLA4, anti-PD-L1, or their respective isotype controls (rat IgG2A and mouse IgG2b). All treatments were administered i.p., three times/week, and started when transplanted tumors reached a size of 0.09 cm2. f, g Tumor growth curves for late treatments (scheduled as in Fig. 4e) of RANK+/+ (f) and RANK−/− (g) tumor cells injected in syngeneic C57BL/6. Each thin curve represents one single tumor. Each thick curve represents the mean of all the tumors that received the specific treatment. Linear regression analysis was performed and a two-tailed p-value was calculated to compare the tumor growth slopes after the specified treatments ***p = 0.0002; ****p < 0.0001).

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