Basophils inhibit early lung metastasis by suppressing regulatory T cells
Abstract Basophils are rare cells best known for their role in allergy but their contribution to cancer remains poorly understood. Here, we found that basophils suppress early lung metastatic seeding in mice by enhancing antitumor CD8 + T cell immunity through inhibition of regulatory T (T reg ) cells. Basophils restrain T reg cells 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 T reg cell suppression and accelerated metastatic seeding in mice. In a prospective double-blind crossover trial of loratadine versus placebo enrolling 40 healthy volunteers ( IRCT20170608034390N14 ), circulating T reg cell frequency (primary outcome) increased following loratadine. Higher blood basophil counts predicted improved survival across human cancers and integrative multiomic analyses identified conserved quiescent (B0) and tumor-associated (B1) basophil states, with B0 predicting favorable outcomes. These findings identify basophils as regulators of early metastatic progression and highlight the basophil–T reg cell axis as a potential therapeutic target.
Authors
- Francisco Javier Quintana (ORCID: https://orcid.org/0000-0001-8156-0736)
- Soroush Setareh (ORCID: https://orcid.org/0000-0002-1095-9499)
- Massimiliano Mazzone (ORCID: https://orcid.org/0000-0001-8824-4015)
- Hadi Esmaily (ORCID: https://orcid.org/0000-0001-6915-6028)
- Nahal Mansouri (ORCID: https://orcid.org/0000-0002-8348-0737)
- Elodie Marcandalli
- Camilo Faust Akl (ORCID: https://orcid.org/0000-0002-5883-4441)
- Yahya Mohammadzadeh (ORCID: https://orcid.org/0009-0006-5720-2617)
- Tommaso Scolaro (ORCID: https://orcid.org/0000-0002-5739-9425)
- Luqing Li
- Bruno Torchia (ORCID: https://orcid.org/0000-0001-5444-4529)
- Niki D. J. Ubags (ORCID: https://orcid.org/0000-0002-0177-4134)
- João Lourenço (ORCID: https://orcid.org/0000-0001-6549-5209)
- Mehrnaz Mesdaghi (ORCID: https://orcid.org/0000-0001-7951-0967)
- Michele De Palma (ORCID: https://orcid.org/0000-0001-9128-5459)
- Nadine Fournier (ORCID: https://orcid.org/0000-0002-9347-7929)
- Marta Manco (ORCID: https://orcid.org/0000-0002-0699-4339)
- Stacey D. Finley (ORCID: https://orcid.org/0000-0001-6901-3692)
- Simge Yucel (ORCID: https://orcid.org/0000-0002-8980-0412)
- Christophe von Garnier (ORCID: https://orcid.org/0000-0003-3585-9176)
- Morgane Fournier
- Anton M Schüle (ORCID: https://orcid.org/0009-0003-3094-9778)
- Ali Ghasemi
- Celine Wyser Rmili
- Shideh Namazi Bayegi
Institutions
- Broad Institute (US)
- University of Southern California (US)
- SIB Swiss Institute of Bioinformatics (CH)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- University of Tehran (IR)
- Centre Hospitalier Universitaire Vaudois (CH)
- VIB-KU Leuven Center for Cancer Biology (BE)
- Swiss Cancer Center Léman (CH)
- Imam Hossein Hospital (IR)
- Shahid Beheshti University (IR)
- École Polytechnique Fédérale de Lausanne (CH)
- Shahid Beheshti University of Medical Sciences (IR)
- BOKU University (AT)
- University of Lausanne (CH)
- KU Leuven (BE)
Publication Details
- Journal
- Nature Cancer
- Published
- 2026-11-03
- DOI
- https://doi.org/10.1038/s43018-026-01257-5
- Primary Topic
- Mast cells and histamine
- Type
- article
- Field-Weighted Citation Impact
- 0.00