Single-cell RNA sequencing of mouse lungs following 4T1-CD9-mCh injection and basophil depletion.

We found that basophils suppress early metastatic seeding in mice by enhancing antitumour CD8⁺ T cell immunity through inhibition of regulatory T cells (Tregs). Basophils restrain Tregs through two complementary mechanisms: mast cell protease 8-mediated cleavage of interleukin-2 receptor α and histamine-mediated activation of the histamine H1 receptor (HRH1).

HRH1 blockade with loratadine abolished Treg suppression, and accelerated metastatic seeding in mice. In a prospective double-blind crossover trial of loratadine versus placebo in healthy volunteers (IRCT20170608034390N14), the primary outcome, circulating Treg frequency, increased following loratadine. Higher blood basophil counts predicted improved survival across human cancers, and integrative multi-omic analyses identified conserved quiescent (B0) and tumour-associated (B1) basophil states, with B0 predicting favourable outcomes.