Abstract 6370: Assessing the effect of blocking CCL2-CCR2 axis on breast cancer brain metastasis

Abstract Among the 300,000 newly diagnosed breast cancer patients every year, 5~20% of them will develop symptomatic brain metastasis, whose 1-year survival rate is lower than 20%. Our group previously reported that brain tumor microenvironment (TME)-mediated PTEN downregulation in brain metastatic tumor cells increases the secretion of the chemokine CCL2, which enhances the infiltration of CCR2+ bone marrow derived myeloid cells, eventually promoting brain metastasis outgrowth. However, the mechanism of CCL2-CCR2 axis promoting brain metastasis is not clear, and the efficacy of targeting either CCR2 or CCL2 remained to be assessed. Here we show that Ccr2 antagonism significantly blocked Ccr2high myeloid cells trafficking in the blood and infiltration into the brain TME. However, Ccr2 antagonism did not sufficiently impede breast cancer brain metastasis in multiple preclinical models. Nevertheless, knocking down CCL2 or targeting CCL2 exhibited significant inhibition of brain metastasis growth. Subsequent analysis of the brain TME through mass cytometry demonstrated dramatically decreased infiltration of both Ccr2high and Ccr2low myeloid cell populations in the CCL2 targeted group, implying that the Ccr2low myeloid cells are also involved in promoting brain metastasis growth. Our data highlights the differential responses between targeting CCR2 or CCL2 in multiple preclinical brain metastasis models, which direct us to explore the function of Ccr2low myeloid cells in regulating brain metastasis progression. Our findings also suggest that carefully choosing between CCR2 or CCL2 as a target to control brain metastasis is important in clinical practice. Citation Format: Yimin Duan, Yutao Qi, Lin Zhang, Xiangliang Yuan, Dihua Yu. Assessing the effect of blocking CCL2-CCR2 axis on breast cancer brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6370.