The role of perivascular macrophages in breast cancer metastasis.1. SPECIFIC OBJECTIVES The microenvironment of solid tumors is composed of both malignant and non-malignant cells and increasing evidence suggests that the fate of malignant cells can potentially be altered by the behavior of surrounding non-malignant cells. It is becoming increasingly clear that modulation of the tumor microenvironment has an important role to play in tumors displaying their full neoplastic potential and therefore it is not uncommon to target surrounding non-malignant cells, particularly immune cells. , as potential therapeutic targets. Over the past decade, the general concept of tumor development has undergone a significant shift in relation to immune cells. New functions involving both immune and protumoral cells have come to the fore. The immune subgroup typically involved in this behavior is the tumor macrophage population. Clinical studies suggest that in almost 80% of solid tumors, the presence of high numbers of macrophages is associated with disease progression and poor prognosis. The tumor microenvironment has been shown to educate infiltrating monocytes to play favorable roles in tumor development and metastasis. But the macrophage population within a tumor microenvironment is quite heterogeneous and little is known about the role of various macrophage subsets in tumor cell dissemination and metastasis. Our laboratory has generated a transgenic mouse strain that allows the identification of a unique subpopulation of tissue-resident macrophages localized in the perivascular space along post-capillary and lymphatic veins (hereafter referred to as macrophages perivascular; PVM) (Fig. 1). We sho...... middle of paper ......amely PVM. The availability of a transgenic mouse strain that facilitates the identification of PVM, in combination with cutting-edge imaging technology, places us in an ideal position to gain new insights into this subset of innate immune cells. Furthermore, we believe that our experiments will increase the knowledge of the contributions of m to the regulation of tumor immunologyReferences:1 Chechlinska, M et al. Systemic inflammation as a confounding factor in cancer biomarker discovery and validation. Comments on nature. Cancer 10, 2-3, (2010).2 Pollard, JW Tumor-formed macrophages promote tumor progression and metastasis. Comments on nature. Cancer 4, 71-78, (2004).3 Wyckoff, JB et al. Direct visualization of macrophage-mediated tumor cell intravasation in breast tumors. Cancer research 67, 2649-2656, (2007).