Tumor-associated macrophages (TAM) are abundant in many types of cancers. Together with other stromalcell types (fibroblasts, neutrophils, mast cells, T cells, dendritic cells, endothelial cells) and matrixcomponents (collagen, fibronectin, glycoproteins) these cells exhibit complex regulatory functions mediatedthrough growth factors, chemokines, cytokines and angiogenesis promoting factors. There is compellingevidence that TAM respond to tumor stimuli with the release of proteolytic enzymes, chemokines, cytokinesand growth factors and have therefore been proposed to be essential to invasion, proliferation, angiogenesisand metastases formation. Recent advances in in vivo imaging have yielded new insights into migration ofhost and cancer cells, however the necessary tools to fully quantify and catalog these interactions are stilllargely missing. The overall goal of this project is therefore to develop novel in vivo imaging agents withspecificity for subtypes of TAM, their monocytic precursors and tissue macrophages. This will be done usingpowerful library approaches and recently developed nanomaterials capable of detection by multiple imagingmodalities and spatial resolutions. In parallel, we will continue the development of imaging agents for otherstromal cells ((myo)fibroblasts, NK cells and T cells) to be used in the Weinberg and Jacks projects. Incollaboration with the Hynes group as well as other macrophage research groups, we will study therecruitment and fate of monocytes/macrophages in tumors. Finally, targeting TAM as a therapeutic strategyagainst cancer is an intriguing concept that needs further study. We will therefore measure the effect ontumor growth and metastatic potential following selective anti-TAM therapy. Specifically, we will ask thefollowing questions: 1) What is(are) the direct precursor(s) of TAM, and is there differential participation ofTAM subsets in primary and metastatic tumors? 2) What is the involvement of TAM during tumor progression(initiation, invasion, angiogenesis and metastasis)? 3) Does elimination of distinct TAM subsets result inmeasurable anti-cancer effects? The developed agents and strategies will be designed to be clinicallytranslatable and should support our previous clinical data in glioma that imaging of TAM can have importantprognostic and therapeutic implications.
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