Lung Cancer Study Identifies Genetic Locus Associated with Survival Response to Immunotherapy

Strategic Insights -

Researchers at Fatebenefratelli Hospital in Milan, Italy, have conducted a genome-wide association study (GWAS) to identify germline variants associated with the response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) patients. The study found that a locus on chromosome 2 was significantly associated with overall survival (OS) in patients treated with ICI.

Key Takeaways:

  • The study identified a locus on chromosome 2 (lead variant: rs111648355) that showed near genome-wide significance (p value=6.3 x 10^(-7)) for OS in patients with NSCLC treated with ICI.
  • Patients with minor alleles of this variant exhibited significantly worse OS (HR=5.1, 95% CI: 2.9 to 9.2).
  • The study highlighted the potential of germline variants as predictive biomarkers of response to ICI.
  • Regulatory effects on genes including MSH2, MSH6, PPP1R21, FBXO11, and STON1 were identified as contributing to the variability in efficacy among individuals.
  • The study concluded that although the results need further validation, they highlight the potential of germline variants as predictive biomarkers of response to ICI.

Statistics:

  • 95% CI for OS: 2.9 to 9.2
  • P value for OS: 6.3 x 10^(-7)
  • HR for OS: 5.1

Sources:

  • NewsRx. New Lung Cancer Study Results from Fatebenefratelli Hospital Described (Regulatory polymorphisms of MSH6, MSH2, FBXO11, and PPP1R21 genes affect survival of patients with immunotherapy-treated lung cancer). Cancer Weekly. [September 16, 2025; p 3663].
  • Journal for ImmunoTherapy of Cancer. Regulatory polymorphisms of MSH6, MSH2, FBXO11, and PPP1R21 genes affect survival of patients with immunotherapy-treated lung cancer. 2025, 13(9). (http://www.immunotherapyofcancer.org/).
  • Fatebenefratelli Hospital. Medical Oncology Unit, Milan, Italy. (Contact: Gabriella Farina, Medical Oncology Unit, Fatebenefratelli Hospital, ASST Fatebenefratelli Sacco, Milan, Italy).