Macrophages in cancer metastasis and drug resistance

Non-malignant host cells forms a dynamic and heterogeneous tumour microenvironment that is critical for disease outcome. Macrophages, a type of innate immune cells, are abundantly found in the tumour microenvironment and enhance malignancy. Our research has been focusing on the role of macrophages in cancer metastasis and response to therapies that are two major challenges to cancer patients in clinic. At distal metastasis sites, our previous studies identified a distinct population of metastasis-associated macrophages (MAMs) that promote tumour cell extravasation, seeding and persistent growth. These macrophages were derived from inflammatory monocytes recruited by CCL2/CCR2 chemokine signaling and directly promote tumour cell extravasation through VEGF production. Our recent studies identified two subsequent signaling pathways that mediate the retention and function of MAMs after recruitment that are critical for breast cancer cell survival and persistent growth during distal metastasis. In another study, we characterized a distinct population of macrophages that promote cancer recurrence following chemotherapy and identified the molecular mechanisms that mediate their function. Together, our studies suggest the therapeutic potential of targeting these pathways in macrophages in treating metastatic disease and enhance the efficacy of anti-cancer chemotherapy.