Figures & data
Figure 1. Targeting a positive feedback loop between EMT-modified cancer cells and TAMs in breast cancer. The chemokine (C-C motif) ligand 18 (CCL18) produced by tumor-associated macrophages (TAMs) induces epithelial-mesenchymal transition (EMT) of tumor cells and enhances granulocyte-macrophage colony stimulating factor (GM-CSF) secretion in a PITPNM3-Pyk2-Src-Raf/PI3K-NFκB dependent manner. Reciprocally, GM-CSF from EMT-altered cancer cells activates monocytes to differentiate into a TAM-like phenotype that secrets CCL18. Neutralization of either GM-CSF or CCL18 breaks this vicious cycle and reduces breast cancer metastasis. Immunotherapies blocking CCL18 in combination with glycolysis inhibitors may inhibit cancer metastasis and attenuate immunosuppression, thereby unleashing anticancer immune responses.
