Turning enemies into allies—reprogramming tumor-associated macrophages for cancer therapy

Checkpoint blockade therapies that target inhibitory receptors on T cells have revolutionized clinical oncology. Antibodies targeting CTLA-4 or the PD-1/PD-1 ligand (PD-L1) axis are now successfully used alone or in combination with chemotherapy for numerous tumor types. Despite the clinical success of checkpoint blockade therapies, tumors exploit multiple mechanisms to escape or subvert the anti-tumor T cell response. Within the tumor microenvironment, tumor-associated macrophages (TAMs) can suppress T cell responses and facilitate tumor growth in various ways, ultimately debilitating clinical responses to T cell checkpoint inhibitors. There is therefore significant interest in identifying biologicals and drugs that target immunosuppressive TAM within the tumor microenvironment and can be combined with immune checkpoint inhibitors. Here, we review approaches that are currently being evaluated to convert immunosuppressive TAM into immunostimulatory macrophages that promote T cell responses and tumor elimination.