Common Asthma Drug May Supercharge Cancer Immunotherapy, Study Finds

Immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 have transformed the treatment of many cancers, yet a significant proportion of patients develop primary or acquired resistance that renders these agents ineffective. Tumors notorious for poor immunotherapy response, such as triple-negative breast cancer (TNBC), ovarian cancer, and melanoma, continue to present urgent unmet needs. A central mechanism driving this resistance is the expansion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), which is a subset of immunosuppressive neutrophils that accumulate in the tumor microenvironment and actively block T-cell–mediated tumor killing.

Despite mounting evidence linking PMN-MDSCs to worse prognoses and ICI failure across multiple tumor types, actionable drug targets within this pathway have remained elusive.^1,2

CysLTR1 as a Tumor-Hijacked Immune Switch

A new study published in Nature Cancer by researchers from the Northwestern University Feinberg School of Medicine has identified cysteinyl leukotriene receptor 1 (CysLTR1) as a critical regulator of tumor-induced emergency myelopoiesis, which is the abnormal overproduction of immunosuppressive neutrophils that cancers exploit to escape immune surveillance.³

CysLTR1 is best known to pharmacists as the receptor blocked by leukotriene receptor antagonists (LTRAs) such as montelukast (Singulair; Merck) in asthma and allergic rhinitis management. In this study, however, investigators discovered that tumors exploit a STAT3-dependent pathway to upregulate CysLTR1 expression on neutrophils, effectively co-opting a normal inflammatory mechanism to drive PMN-MDSC expansion and shield themselves from immune attack.³

“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,” Bin Zhang, MD, PhD, senior study author and the Johanna Dobe Professor of Cancer Immunology at Northwestern University Feinberg School of Medicine, said in a news release.⁴

Key Findings

Using mouse models of TNBC, melanoma, ovarian, colon, and prostate cancer, as well as human immune cells and publicly available patient cancer datasets, the Northwestern team demonstrated several pivotal findings.^3,4

When CysLTR1 was genetically ablated or pharmacologically blocked with montelukast, tumor growth slowed, survival improved, and ICI response was restored even in tumors already resistant to anti-PD-1 therapy. Crucially, the mechanism went beyond simple PMN-MDSC depletion, finding that blocking CysLTR1 reprogrammed immunosuppressive neutrophils toward an antitumor phenotype. This disarming effect was mediated through transcriptional rewiring involving 2 key factors—MXD1 and NFE2—that govern myeloid progenitor commitment and neutrophil granule synthesis.³

Analysis of human tumor samples and large cancer datasets further showed that patients with elevated CysLTR1 activity tended to have worse survival and reduced responsiveness to immunotherapy across multiple cancer types.⁴

“Importantly, instead of simply removing these harmful white blood cells, we were able to reprogram them into cells that support immune attack,” Zhang said. “That means we’re not just targeting the cancer; we’re retraining one type of abundant immune cells in the body to fight the tumor again.”⁴

Pharmacist Perspective: A Drug Already on the Shelf

For pharmacy professionals, the translational potential of these findings is particularly noteworthy. Montelukast is an FDA-approved, orally administered agent with a well-established safety profile spanning decades of clinical use. This existing approval and pharmacovigilance data could dramatically shorten the typical timeline from preclinical discovery to patient trials.

Separately, a 2025 case report described sustained disease stabilization for more than 12 months in a patient with a CYSLTR2-mutant metastatic uveal melanoma treated off-label with montelukast 10 mg daily, which represents the first published clinical signal for leukotriene receptor antagonism in a solid tumor harboring a CysLTR pathway mutation.⁵

Implications and Next Steps

The study authors noted that the next priorities include confirming the mechanism in patient populations, identifying predictive biomarkers to determine who will benefit most, and optimizing combination regimens with existing ICIs, particularly for aggressive cancers such as TNBC, where therapeutic options remain limited.⁴

As pharmacists increasingly serve as integral members of oncology care teams, awareness of emerging combination strategies, especially those repurposing commonly dispensed agents, will be essential for counseling patients and supporting clinical trial recruitment.

REFERENCES

1. Shi X, Deng W, Pan Y, Chen Y, Wang Y and Wu J (2025) Overcoming resistance to immune checkpoint inhibitor in non-small cell lung cancer: the promise of combination therapy. Front Immunol. 16:1691980. doi:10.3389/fimmu.2025.1691980

2. He S, Zheng L, Qi C. Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy. Mol Cancer. 2025 Jan 8;24(1):5. doi:10.1186/s12943-024-02208-3.

3. Tang H, Xie P, Ahn J, et al. Targeting cysteinyl leukotriene receptor 1 reprograms tumor-promoting myelopoiesis and overcomes immune checkpoint therapy resistance. Nat Cancer. 2026. doi:10.1038/s43018-026-01174-7

4. Common asthma drug shows promise against aggressive cancers. News release. EurekAlert! May 19, 2026. Accessed May 20, 2026. https://www.eurekalert.org/news-releases/1128518

5. Smarsly D, Kreuzberg N, Langhorst C, et al. Montelukast as a novel therapeutic approach in metastatic uveal melanoma harboring a CYSLTR2 mutation: a translational case report. ESMO Open. 2026;11(1):105921. doi:10.1016/j.esmoop.2025.105921.