Studying Interactions between Myeloid Cells and CAR T Cells <em>In Vitro</em> and <em>In Vivo</em>

Chimeric antigen receptor T (CART) cell therapy has led to remarkable clinical successes treating hematological malignancies. However, most patients relapse within 1-2 years. Several mechanisms leading to CART resistance have been identified, including T cell inhibition by immunosuppressive myeloid cells. Growing evidence has shown that monocytes and macrophages in the tumor microenvironment (TME) contribute to poor CART performance and clinical outcomes. Preclinical models to study interactions between human macrophages and CART cells are limited. Here, we discuss approaches to understand the impacts from human macrophages on CART cells both in vitro and in vivo. We describe in vitro coculture models to show that immunosuppressive macrophages inhibit CART functions. Additionally, we report a xenograft model where human macrophages and tumor cells are subcutaneously engrafted in NSG mice to study M2-like macrophage interactions with CART cells and tumor cells. These models can be used to evaluate roles of macrophages in the TME and test macrophage-targeted cancer immunotherapies.