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New analysis introduced identifies interferon-induced transmembrane protein 3 (IFITM3) as a crucial regulator of immunotherapy sensitivity in small cell lung most cancers (SCLC), providing a promising new avenue for overcoming resistance to PD-1/PD-L1 checkpoint blockade.
The analysis was introduced on the Worldwide Affiliation for the Examine of Lung Most cancers 2025 World Convention on Lung Most cancers (WCLC).
SCLC tumors are usually characterised by low expression of main histocompatibility advanced class I (MHC-I), which impairs immune recognition and response.
Researchers from the Shanghai Pulmonary Hospital and the College of Pittsburgh have found that IFITM3 enhances MHC-I expression by activating NLRC5, a key transcriptional regulator, and selling its nuclear translocation. This impact improves antigen presentation and boosts CD8+ T cell infiltration and cytotoxicity.
“Our study shows that IFITM3 plays a pivotal role in shaping tumor immunogenicity in SCLC,” mentioned Dr. Xinyu Liu of Shanghai Pulmonary Hospital, Tongji College Faculty of Medication, China. “It may serve both as a predictive biomarker for immunotherapy response and a novel therapeutic target.”
Dr. Liu introduced various vital findings:
Robust correlation between IFITM3 and MHC-I expression in a number of real-world SCLC cohorts.
IFITM3 overexpression upregulated antigen presentation pathways and elevated CD8+ T cell infiltration.
IFITM3 expression predicted improved progression-free survival in sufferers receiving chemoimmunotherapy.
A novel compound, ethyl gallate (EG), induced IFITM3 and sensitized tumors to PD-1 blockade in preclinical fashions.
“Our study suggests that pharmacological induction of IFITM3 could represent a new strategy to improve clinical outcomes for patients with SCLC. Future clinical research may validate IFITM3 as both a biomarker and a therapeutic adjunct to current immunotherapy regimens,” Dr. Liu reported.
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Worldwide Affiliation for the Examine of Lung Most cancers
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New analysis identifies IFITM3 as key driver of immunotherapy response in small cell lung most cancers (2025, September 9)
retrieved 9 September 2025
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