Abstract: As disclosed herein, SIRP? is integral to immuno-evasion by many different cancer types as well as cancer resistance to therapies, and reducing SIRP? levels on can bolster antigen acquisition, processing, and presentation, decrease TME immunosuppression and thereby promote tumor-specific T cell activation to eliminate tumors and generate an adaptive immune response consisting of memory T cells, circulating antibodies, and plasma cells, all of which may be specific for neo-antigens in the original cancer. Therefore, disclosed are activated SIRP?low macrophages that are useful for treating cancers.