An asthma drug that has been approved for decades could improve the treatment of aggressive cancers. US researchers have discovered that tumors use the CysLTR1 receptor to trick the immune system and turn immune cells into allies. Blocking this switch with the active ingredient montelukast slowed tumor growth in animal models and improved the effectiveness of immunotherapy.

Scientists at Northwestern University in Chicago report in the journal “Nature Cancer” (published on May 19) that many types of cancer – including triple-negative breast cancer, melanoma, ovarian, colorectal and prostate cancer – abuse the CysLTR1 receptor. It controls the formation of tumor-promoting neutrophil granulocytes, which weaken the immune system and hinder the effect of immune checkpoint inhibitors.

Mouse models and studies of human tumor samples and immune cells showed that when CysLTR1 was genetically switched off or pharmacologically blocked, tumor growth slowed down, survival time increased, and sensitivity to immunotherapy returned even in previously resistant tumors. Instead of simply eliminating the harmful neutrophils, they could be reprogrammed into immune-promoting cells by blocking them.

Analyses of large patient databases also showed that high CysLTR1 activity is associated with poorer survival and lower response to immunotherapies.

Since montelukast (Singulair) is already available as a safe and approved drug, clinical trials could follow quickly. The researchers led by senior author Dr. Bin Zhang see an urgent need for new combination approaches, especially in the case of difficult-to-treat cancers such as triple-negative breast cancer.

The study was funded in part by the National Institutes of Health and the National Cancer Institute.

Original Paper:

Targeting cysteinyl leukotriene receptor 1 reprograms tumor-promoting myelopoiesis and overcomes immune checkpoint therapy resistance | Nature Cancer

Editor: X-Press Journalistenbüro GbR

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