Regulatory T cells (Treg cells) are controlled by a raft of transcription factors besides Forkhead box protein 3 (FOXP3). As detailed in this Review, these accessory transcription factors act alone or together with FOXP3 to coordinate Treg cell specification and function, and account for heterogeneity of niche-specific Treg cells.

Recent studies have highlighted the diversity and distinct nature of regulatory T cells in the intestine, where they must balance a multitude of signals from the microbiota and the diet to ensure immune homeostasis. But questions and controversies remain over their origins and regulation, as discussed here.

Probiotic gut bacteria can translocate to and persist in melanomas where they stimulate antitumour CD8+ T cells through the production of immunomodulatory metabolites.

In this Perspective, Honjo and co-workers describe the discovery of PD1 and its journey to become a major target for cancer immunotherapy. It discusses the complex regulatory systems that govern PD1 expression as well as recent insights into PD1 function and the mechanisms of PD1-blocking therapies.