Figure 2. Inhibition of tumor recruitment of CXCR4+ TEMs increases the therapeutic efficacy of CA4P.
(A) CXCL12 expression, determined by immunofluorescence staining (see Supplemental Figure 3), was increased in MMTV-PyMT tumors 24 hours after injection with 50 mg/kg CA4P. (B and C) Flow cytometric analysis of dispersed MMTV-PyMT tumors shows that (B) the majority of F4/80+TIE2+ TEMs express CXCR4 and the MFI for CXCR4 is higher for TEMs than TIE2– TAMs and (C) CXCR4 expression/TEM is upregulated after CA4P treatment. (D) The CXCR4 inhibitor, AMD-3100, inhibits recruitment of TEMs, but not TIE2– TAMs, to MMTV-PyMT tumors and increases CA4P-induced tumor necrosis. n > 5 mice per group. *P < 0.05; **P < 0.01. (E) Twice daily i.p. injections of 5 mg/kg AMD-3100 (for the period indicated) enhanced the effects of 3 daily i.p. injections of 50 mg/kg CA4P on the growth of N202 tumors. Statistical analysis in E employed the nonlinear mixed effects model described in the Supplemental Methods.