New Research Identifies IFITM3 as Key Driver of Immunotherapy Response in Small Cell Lung Cancer

(Barcelona, Spain September 9, 2025 1 p.m. CEST / UTC +2) — New research presented identifies interferon-induced transmembrane protein 3 (IFITM3) as a critical regulator of immunotherapy sensitivity in small cell lung cancer (SCLC), offering a promising new avenue for overcoming resistance to PD-1/PD-L1 checkpoint blockade.

The research was presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer (WCLC).

SCLC tumors are typically characterized by low expression of major histocompatibility complex class I (MHC-I), which impairs immune recognition and response. Researchers from the Shanghai Pulmonary Hospital and the University of Pittsburgh have discovered that IFITM3 enhances MHC-I expression by activating NLRC5, a key transcriptional regulator, and promoting its nuclear translocation. This effect 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,” said Dr. Xinyu Liu of Shanghai Pulmonary Hospital, Tongji University School of Medicine, China. “It may serve both as a predictive biomarker for immunotherapy response and a novel therapeutic target.”

Dr. Liu presented a number of significant findings:

• Strong correlation between IFITM3 and MHC-I expression in multiple real-world SCLC cohorts.
• IFITM3 overexpression upregulated antigen presentation pathways and increased CD8⁺ T cell infiltration.
• IFITM3 expression predicted improved progression-free survival in patients receiving chemoimmunotherapy.
• A novel compound, ethyl gallate (EG), induced IFITM3 and sensitized tumors to PD-1 blockade in preclinical models.

“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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About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 10,000 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.

About the WCLC:
The WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting nearly 7,000 researchers, physicians, and specialists from more than 100 countries. The goal is to increase awareness, collaboration and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit https://wclc.iaslc.org/.