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The presence of some innate immune cell types in developing neoplasms provides a significant pro-tumor advantage. Myeloidlineage immune cells, such as tumor-associated macrophages (TAMs) and immature myeloid-derived cells/monocytes, promote tumor development by exerting pro-tumor activities including activating angiogenic programs, suppressing anti-tumor immunity, and enhancing migratory and metastatic properties of malignant cells. We have now established in both murine models and human patients that exposure to neoadjuvant chemotherapy induces the recruitment of myeloid populations, including tumor-associated macrophage. Using the dependency of this population on the CSF1/CSF1R pathway for recruitment to the tumor microenvironment, we have demonstrated that preventing macrophage influx improves the response of transgenic mice to chemotherapy, resulting in lower primary tumor and pulmonary metastatic burden. Despite this success, human breast cancers are infiltrated by a wider variety of myeloid populations, for example mast cells, that may share overlapping functions with macrophages but that are not dependent on the CSF1/CSF1R pathway. Identifying common molecular pathways mediating chemoresistance may therefore improve the chance and/or efficacy of clinical translation. Along these lines, preliminary data suggests that CSF1/CSF1R blockage selectively reduces infiltration of an IL-10 producing subpopulation of macrophages, and that blockade of IL-10 signaling may be similarly efficacious to direct macrophage targeting. These studies therefore hold great potential for improving the rate of pathological complete response in patients and prolonging survival.