Asthma drug pathway may help restore cancer immunotherapy responsiveness

Northwestern Medicine researchers have found that cancers may exploit cysteinyl leukotriene receptor 1, a molecule best known for its role in asthma and inflammation, to recruit immune-suppressive neutrophils and evade immunotherapy

A drug class widely used to treat asthma and allergies could help to improve immunotherapy responses in aggressive cancers, according to a study by Northwestern Medicine, Chicago, USA, that has identified how tumours co-opt common white blood cells to suppress anti-cancer immunity.

The findings, based on mouse models, human immune cells, human tumour samples and large cancer datasets, suggest that cysteinyl leukotriene receptor 1 (CysLTR1) may offer a practical therapeutic route in difficult-to-treat malignancies, including triple-negative breast cancer, in which immunotherapy often delivers limited benefit.

CysLTR1 is best known for its role in asthma, allergy and inflammatory signalling. Drugs that block this receptor, including montelukast have been prescribed for decades to treat asthma and related allergic conditions. The team has now reported that several cancers appear to exploit the same pathway to resist treatment.

The researchers found that tumours used CysLTR1 to increase a population of neutrophils, a highly abundant class of white blood cell that normally forms part of the body’s first-line immune defence. In the tumour environment, however, these cells can be diverted from protective activity and converted into immune-suppressive cells that help cancers to grow and evade treatment. The study indicated that CysLTR1 acted as a molecular switch in this process.

“When we turned off this switch, either genetically or with existing drugs, we not only slowed tumour growth but also helped the immune system recover its ability to fight the cancer,” said Dr Bin Zhang, senior author of the study and ‘Johanna Dobe Professor of Cancer Immunology’ at the Northwestern University Feinberg School of Medicine.

Zhang and colleagues used a broad experimental strategy that combined mouse cancer models, human immune-cell studies, tumour-sample analysis and interrogation of public cancer datasets. The mouse studies included models of triple-negative breast cancer, melanoma, ovarian cancer, colon cancer and prostate cancer. The researchers either removed CysLTR1 genetically or blocked its activity with drugs such as montelukast.

Across several mouse models, inhibition of the pathway slowed tumour growth, improved survival and restored response to immunotherapy. Notably, this effect was seen even in tumours that had already stopped responding to treatment, a finding that may be particularly relevant to cancers with acquired resistance to immune checkpoint blockade.

The team also examined human immune cells and found that CysLTR1 blockade prevented the development of neutrophils with immune-suppressive properties. This suggested that the approach did not merely deplete a harmful cell population but altered the behaviour of an abundant immune-cell type within the tumour microenvironment.

“Importantly, instead of simply removing these harmful white blood cells, we were able to reprogramme them into cells that support immune attack,” Zhang said.

“That means we’re not just targeting the cancer, we’re re-training one type of abundant immune cells in the body to fight the tumour again,” he added.

Further analysis of human tumour samples and public cancer datasets supported the experimental findings. The researchers found evidence that higher CysLTR1 activity was associated with poorer survival and weaker immunotherapy responses across multiple cancer types. This strengthened the case that the pathway may have broad relevance beyond a single tumour class.

Because CysLTR1-blocking drugs such as montelukast have already received approval from the US Food and Drug Administration, the findings may offer a comparatively rapid route towards early clinical testing. However, the study does not mean that patients should use asthma medicines as cancer treatment outside a properly designed clinical trial. The next step will be to establish whether the mechanism operates in patients and whether drug combinations can safely improve outcomes.

“We may be able to test it quickly and safely in cancer patients to improve immunotherapy. Especially in aggressive cancers, like triple-negative breast cancer, where novel options are urgently needed,” Zhang said.

“The next steps are to confirm this mechanism in patients, identify who will benefit most, optimise how we use these drugs especially in combination with immunotherapy, and begin carefully designed clinical trials,” Zhang concluded.

For further reading please visit: 10.1038/s43018-026-01174-7