Macrophages as regulators of tumour immunity and immunotherapy

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. In this Review, DeNardo and Ruffell describe how macrophages shape local immune responses in the tumour microenvironment to both suppress and promote immunity to tumours. The authors also discuss the potential of targeting tumour-associated macrophages to enhance antitumour immune responses.