Denardo and Ruffell review the role of tumor-associated macrophages in tumor immunity. This heterogeneous myeloid population can be exploited by many factors in the TME (hypoxia, fibrosis, tumor- and lymphocyte-derived signals) to promote angiogenesis, immunosuppression, and metastasis. They explore the direct and indirect mechanisms by which macrophages suppress antitumor immune functions or prevent immune cell infiltration, as well as ways to therapeutically target macrophages (depletion, prevention of recruitment, repolarization) to improve antitumor immunity.
Macrophages are critical mediators of tissue homeostasis, with tumours distorting this proclivity to stimulate proliferation, angiogenesis and metastasis. This had led to an interest in targeting macrophages in cancer, and preclinical studies have demonstrated efficacy across therapeutic modalities and tumour types. Much of the observed efficacy can be traced to the suppressive capacity of macrophages, driven by microenvironmental cues such as hypoxia and fibrosis. As a result, tumour macrophages display an ability to suppress T cell recruitment and function as well as to regulate other aspects of tumour immunity. With the increasing impact of cancer immunotherapy, macrophage targeting is now being evaluated in this context. Here, we discuss the results of clinical trials and the future of combinatorial immunotherapy.