Credit: CC0 Public Domain

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:

"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.