Basophils in cancer: a surprising barrier to early metastasis

Basophils in cancer may play a protective role that has little to do with their familiar involvement in allergies. In mouse experiments, these rare immune cells helped prevent cancer cells from establishing themselves in the lungs. Removing basophils made early metastatic spread more pronounced. Blocking one of their signaling pathways with the common allergy medication loratadine weakened that protection.

The findings, published in Nature Cancer on November 3, 2026, connect three areas of biology that are rarely discussed together: allergic inflammation, antitumor immunity, and metastatic colonization.

The timing of the immune response turned out to be particularly important.

Protection at the earliest stage

Basophils are rare white blood cells containing histamine and other signaling molecules involved in allergic reactions and defense against parasites.

Their role in cancer has long been difficult to interpret. Some studies have suggested that basophils support antitumor immunity, while others have implicated them in processes that help established tumors grow.

The research team, led by scientists at the Swiss Federal Institute of Technology in Lausanne, focused on a specific point in cancer progression: the moment when malignant cells first establish themselves in the lungs.

The investigators selectively depleted basophils in several mouse models involving breast and lung cancer cells. The result was increased cancer cell accumulation in the lungs and, with longer observation, more metastatic nodules.

They then performed the reverse experiment. Transferring basophils into mice reduced the early seeding of lung tissue by cancer cells.

Timing provided an important clue.

When basophils were eliminated before cancer cells reached the lungs, metastatic seeding increased. But removing them seven days after tumor cell injection no longer produced a detectable effect on lung colonization.

This suggests that basophils are particularly important during the initial establishment of metastatic cells, rather than throughout every stage of metastatic growth.

Most of these experiments used intravenously introduced cancer cells, which allows investigators to isolate the lung-colonization stage but does not reproduce the entire natural metastatic process. Supporting results were also obtained in a model with a primary mammary tumor.

How allergy-associated cells release the immune brakes

The central mechanism involved regulatory T cells, commonly called Tregs.

Under normal conditions, these cells perform an essential function: they prevent excessive immune responses and reduce the risk of damage to healthy tissue.

Cancer can exploit the same regulatory system.

Within tumors, Tregs may suppress CD8+ T cells, the immune cells capable of recognizing and killing malignant cells.

The researchers found that basophils interfere with this suppression through two complementary pathways.

The first involves histamine.

Usually associated with itching, swelling, and other allergy symptoms, histamine also activates H1 receptors on regulatory T cells. In these experiments, that signaling increased cellular stress and promoted Treg apoptosis, or programmed cell death.

The second pathway was more unexpected.

Basophils produce an enzyme called MCPT8 that can cleave part of CD25, a protein on the surface of regulatory T cells. CD25 is a component of the interleukin-2 receptor, which helps sustain Treg survival and function.

By disrupting CD25, basophils weakened the signaling that supports these cells.

With Treg-mediated suppression reduced, CD8+ T cells could proliferate more effectively and kill tumor cells.

The two processes operated in parallel. One depended on histamine signaling through H1 receptors, while the other involved direct cell contact and enzymatic cleavage of CD25.

Why loratadine matters

The investigators used loratadine, a widely available H1 antihistamine, to test the importance of histamine signaling.

In cell experiments, loratadine reduced the ability of basophils to suppress regulatory T cells.

In mice, treatment was associated with increased Treg abundance, weaker antitumor CD8+ T-cell activity, and greater early metastatic seeding in the lungs.

This is one of the study's most striking observations.

It does not, however, establish that loratadine increases cancer risk in humans.

The animal experiments used specific cancer models and controlled treatment conditions. Moreover, previous clinical observational studies have reported conflicting associations between antihistamine use and cancer outcomes, including potentially favorable associations in some settings.

To examine whether the immune effects might extend to humans, the researchers conducted a randomized, double-blind crossover trial involving 40 healthy volunteers aged 20 to 30.

Participants received either loratadine at 10 mg daily or placebo for 21 days, followed by the alternate treatment.

Following participant withdrawals and missed blood collections, 29 loratadine samples and 30 placebo samples were available. Complete paired analyses included 25 participants.

The proportion of cells classified as regulatory T cells increased significantly after loratadine compared with placebo.

There is an important methodological qualification. In this clinical trial, the investigators identified these cells using CD4 and CD25 markers without additional FOXP3 confirmation. Because CD25 is also expressed by other activated T cells, this approach is less specific than a more comprehensive Treg identification strategy.

The trial was small, treatment was brief, and cancer outcomes were not measured. Its findings therefore provide no basis for changing prescribed antihistamine treatment or concluding that loratadine promotes cancer in humans.

Evidence from people with cancer

The researchers also examined retrospective data from 11,164 people with cancer treated at Lausanne University Hospital.

Patients with higher circulating basophil counts tended to have better survival. This association appeared across several cancer types, including breast and lung cancer.

But an association is not proof of a protective effect.

The retrospective analysis could not eliminate confounding from differences in disease characteristics, medications, comorbidities, or other clinical factors.

A further discovery helped explain why the role of basophils might change over time.

By integrating gene-expression and protein data, the researchers identified two broad basophil states.

The B0 state was characteristic of healthy tissues and was associated with more favorable cancer outcomes. In tumor environments, basophils increasingly adopted a different program, designated B1.

B1 basophils retained their ability to suppress Tregs but also produced more IL-4 and IL-13, signaling molecules that can reshape other immune cells.

In laboratory experiments, substances released by these tumor-associated basophils promoted an M2-like macrophage phenotype, which may support tumor-associated immune regulation.

This provides a possible explanation for seemingly contradictory findings from earlier studies: basophils may help defend against metastatic seeding at an early stage while acquiring different functions as tumors develop.

The key contribution of this study is a defined mechanism through which basophils restrict the establishment of cancer cells in mouse lungs. The surprising part is that the same cells and signaling molecules long associated with allergic responses also participate in this early antitumor defense.