ArticleMolecular cancer2025
IFITM3 enhances immunosensitivity via MHC-I regulation and is associated with the efficacy of anti-PD-1/-L1 therapy in SCLC.
Article in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Biomimetic co-delivery nanoplatform overcomes CAF- and TAM-induced immunosuppression to augment therapeutic efficacy against triple-negative breast cancer.International journal of pharmaceutics: X · 2026Article
- Interferon-induced transmembrane (IFITM) proteins at the tumour-immune interface: A four-axis framework for their context-dependent roles.Clinical and translational medicine · 2026Review
- Interferon-induced transmembrane proteins in cancer and virus biology: a membrane perspective.mBio · 2026Review
- Identification ofMolecular medicine reports · 2026Article
- Article
- Baseline PD-L1 expression on circulating immune cells as a predictor of survival and immune-related adverse events in extensive-stage small-cell lung cancer patients treated with durvalumab and carboplatin-etoposide (NCT04712903 Trial).Journal of translational medicine · 2026Observational
- Article
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Annotation-free prediction of immunotherapy response in melanoma using single-cell transcriptomic data.PloS one · 2026Article
- Targeted nanoparticle-mediated Co-delivery of IFITM3 KO and ponatinib reverses TKI resistance in chronic myeloid leukemia.Frontiers in pharmacology · 2026Article
- Interferon-induced transmembrane proteins: membrane gatekeepers of fusion and infection.Frontiers in cellular and infection microbiology · 2026Review
- The DDR-immune fitness score: a biomarker for guiding parp and immunotherapy synergy in extensive-stage small cell lung cancer.Frontiers in oncology · 2025Review
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Authors and funding
15 authors.
Funding
Abstract
backgroundMost small cell lung cancer (SCLC) patients exhibit resistance to immune checkpoint inhibitors (ICIs) and demonstrate downregulation of major histocompatibility complex class I (MHC-I) molecules. This study aimed to elucidate the regulatory mechanisms underlying MHC-I expression and potential combination strategies.
methodsSingle-cell and bulk RNA sequencing data from SCLC patients were analyzed. Clinical data from SCLC patients treated with PD-1/PD-L1 inhibitors were used to investigate the associations between treatment efficacy and IFITM3 expression. In vitro and in vivo functional studies were conducted to evaluate the role and mechanisms of IFITM3 in modulating tumor sensitivity to PD-1 inhibitors.
resultsIntegrative analysis of multiple real-world SCLC cohorts confirmed a significant positive association between IFITM3 expression and MHCI. IFITM3 overexpression upregulated MHC-I-related genes, enriched antigen presentation pathways, and increased CD8+ T-cell infiltration and cytotoxicity. Elevated IFITM3 expression was significantly associated with prolonged progression-free survival (PFS) in patients receiving chemoimmunotherapy but not in those treated with chemotherapy alone. Additionally, patients with high H-scores for IFITM3, as determined by immunohistochemistry, demonstrated better clinical outcomes with chemoimmunotherapy. Inducing IFITM3 expression directly or through treatment with ethyl gallate (EG), an IFITM3 inducer, effectively sensitized tumors to PD-1 blockade in SCLC mouse models. Mechanistic studies revealed that IFITM3 upregulates NLRC5, a key transcriptional activator of MHC-I, facilitating its nuclear translocation and thereby increasing MHC-I levels.
conclusionsIFITM3 is associated with MHC-I expression and can predict the efficacy of anti-PD-1/-L1 therapy in SCLC patients. IFITM3 inducers potently improved the efficacy of anti-PD1 monotherapy in SCLC.
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