Tumours can turn one of the body’s everyday immune cells into an ally. Researchers at Northwestern University say they have found a switch behind that process, and an asthma drug that already has US approval may help turn it off.
The team said many cancers use a molecule called CysLTR1 to resist treatment. They found tumours increase a group of white blood cells called neutrophils, which then help the cancer grow. The researchers said CysLTR1 acts as an on and off switch for that process.
“When we turned off this switch, either genetically or with existing drugs, we not only slowed tumor growth, but also helped the immune system recover its ability to fight the cancer,” study senior author Professor Bin Zhang said.
The researchers from Northwestern’s Feinberg School of Medicine combined experiments in mouse models, human immune cells and human tumour samples with analysis of large patient cancer datasets. The mouse studies included models of triple-negative breast cancer, melanoma, ovarian cancer, colon cancer and prostate cancer.
They either genetically removed CysLTR1 or blocked it using drugs such as montelukast, commonly known by the brand name Singulair. In several mouse models, blocking the pathway slowed tumour growth, improved survival and restored response to cancer-killing immunotherapy. The team said that happened even in tumours that had already stopped responding to treatment.
The findings, published in Nature Cancer, also showed in human immune cells that blocking CysLTR1 prevented the formation of immune-suppressing neutrophils.
“Importantly, instead of simply removing these harmful white blood cells, we were able to reprogram them into cells that support immune attack.
“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 tumor again,” Professor Zhang said.
In analyses of human tumour samples and public cancer datasets, the scientists found patients with higher CysLTR1 activity tended to have worse survival and poorer response to immunotherapy across multiple cancer types.
Professor Zhang said the use of an already approved drug could help move the work into clinical testing.
“We may be able to quickly and safely test it in cancer patients to improve immunotherapy, especially in aggressive cancers, like triple-negative breast cancer, where new options are urgently needed.
“The next steps are to confirm this mechanism in patients, identify who will benefit most, optimize how we use these drugs especially in combination with immunotherapy, and begin carefully designed clinical trials.”
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