Contribution of ontogeny to the role of tumor-associated macrophages in disease:
Macrophages represent the most abundant phagocytes in tissue. As such, in tumors, they are responsible for handling the major proportion of antigen and debris developing from tumor cells; the handling of these antigens can therefore impact the induction or maintenance of an anti-tumor immune response.
Work from our lab has played a foundational role in elucidating distinct ontogenies of tissue macrophages throughout the body, in particular in demonstrating how macrophage precursors seed organs such as the brain and lungs during embryonic development and self-maintain locally throughout life. Macrophages of embryonic ontogeny have distinct phenotypic and functional properties compared to macrophages derived from adult myelopoiesis in the context of tissue inflammation. We are therefore invested in understanding the extent to which embryonic macrophages populate tumor lesions compared to their monocyte-derived counterparts, as well as in elucidating the consequences of this distinction with respect to the organization of the tumor microenvironment, the development of an anti-tumor immune response, and tumor growth. By targeting macrophages using genetic depletion, depleting antibodies, and macrophage-directed CAR-T cells, we are identifying the roles for these macrophage subpopulations and therapies to leverage these differences.