Mast cells

Mast cells are complex immune cells with varied functions. This Perspective explores the divergent phenotypes and functions of mast cells resulting from both their hard-wired ‘nature’ defined by their ontogeny and the ‘nurture’ they receive within specialized tissue microenvironments.

In a phase 1 trial of patients with advanced systemic mastocytosis, avapritinib, a selective KIT inhibitor, was generally well tolerated, elicited durable clinical responses and led to reductions in mast cell disease burden.

In a prespecified interim analysis of a pivotal phase 2 trial, avapritinib, a selective KIT inhibitor, elicited robust clinical and molecular responses, was generally well tolerated and led to improved patient-reported outcomes in patients with advanced systemic mastocytosis.

Fenebrutinib, an oral Bruton’s tyrosine kinase inhibitor, reduces disease activity in patients with chronic spontaneous urticaria refractory to antihistamines, suggesting that this treatment type could be an alternative to standard of care anti-IgE therapy.

Immune checkpoint therapies (ICT) are promising for treating various cancers, but response rates vary. Here the authors show, in mouse models, that tumor-infiltrating mast cells colocalize with regulatory T cells, coincide with local reduction of MHC-I and CD8 T cells, and is associated with resistance to ICT, which can be reversed by c-kit inhibitor treatment.