Cell-intrinsic view of the aryl hydrocarbon receptor in tumor immunity

Emerging insights into aryl hydrocarbon receptor (Ahr) biology have revealed its key role in regulating mammalian host immunity and tissue homeostasis. Depending on the context, immune cells can play either a pro- or antitumor role in cancer. Ahr has classically been viewed as protumorigenic; however, given recent advances in our understanding of Ahr functions, especially in the immune system, this view requires reassessment. Moreover, given its cell type-specific activity, therapeutic exploitation of the Ahr pathway should be cautiously considered. We describe the function of Ahr in different immune cells, and connect with their roles in cancer immunology. In addition, we discuss clinical perspectives of how recent advances in our understanding of Ahr biology might be therapeutically applied to improve cancer outcomes. The aryl hydrocarbon receptor (Ahr) is a cell type-specific regulatory factor that can have both pro- and antitumor roles depending on the context and immune cell subset.Owing to the relatively wide expression pattern of Ahr in mice and humans, the effects of systemic treatment with Ahr ligands or antagonists in cancer can be potentially confounding, thus necessitating careful interpretation of experimental results.The cell-intrinsic impact of Ahr on immune versus cancer cells in tumors requires further investigation to allow the rational development of effective therapeutics.An exciting link between cancer and the microbiota has been described: some bacteria can effectively support antitumor immunity, and some of these can produce ligands that activate Ahr.