Basophils limit early lung metastasis in mice by suppressing regulatory T cells

Researchers investigated whether basophils influence early metastatic spread through effects on regulatory T (Treg) cells. In mouse models of breast and lung cancer, basophil depletion increased cancer-cell seeding in the lungs; depletion also increased metastatic burden in a longer-follow-up breast cancer model. The team examined the proposed mechanisms and analyzed human cancer data. They also conducted a prospective, double-blind crossover trial of loratadine versus placebo in 40 healthy volunteers, with circulating Treg-cell frequency as the primary outcome.

In mice, basophils restrained Treg cells through mast cell protease 8-mediated cleavage of the IL-2 receptor α subunit and histamine signaling through HRH1. Blocking HRH1 with loratadine abolished Treg suppression and accelerated metastatic seeding. In the volunteer trial, circulating Treg-cell frequency increased after loratadine. Higher blood basophil counts and a quiescent basophil state were associated with more favorable survival in analyses across human cancers.

The findings suggest a role for basophils in early metastatic control, but the evidence does not establish a cancer-treatment benefit in people. The loratadine trial involved healthy volunteers and measured an immune-cell endpoint, not cancer outcomes; the metastasis experiments were in mice. The results do not support changing loratadine use or cancer care.