Evidence map›Paper›PMID 40611157›Full record

ArticleMolecular cancer2025

IFITM3 enhances immunosensitivity via MHC-I regulation and is associated with the efficacy of anti-PD-1/-L1 therapy in SCLC.

Yanan Cui, Tianyu Qiu, Jiale Wang, Xinyu Liu, Libo Luo, Jizhong Yin, Xinxin Zhi, Wanying Wang, Gaohua Feng, Chunyan Wu and 5 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Identification ofMolecular medicine reports · 2026
    Article
  5. iScience · 2026
    Article
  6. Observational
  7. Article
  8. The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026
    Review
  9. Article
  10. Article
  11. Review
  12. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Yanan Cui *Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Tianyu Qiu *Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Jiale Wang *Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Xinyu LiuDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Libo LuoDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Jizhong YinDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Xinxin ZhiDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Wanying WangDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Gaohua FengDepartment of Pulmonary and Critical Care Medicine, Zhangjiagang Hospital of Traditional Chinese Medicine, Suzhou, China.
Chunyan WuDepartment of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Zhikai ZhaoDepartment of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Hua ZhangHillman Cancer Center, UPMC, Pittsburgh, PA, 15232, USA.
Fei LiDepartment of Pathology, Frontier Innovation Center, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. li_fei@fudan.edu.cn.
Fengying WuDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China. fywu@163.com.
Shengxiang RenDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China. harry_ren@tongji.edu.cn.

Funding

National Basic Research Program of China 2022YFA1103900National Key Clinical Specialty Discipline Construction Program of China Establishment and Application of a Precision Diagnosis and Treatment System for Chest TumorsNational Natural Science Foundation of China 82373319Science and Technology Commission of Shanghai Municipality 21XD1423200Shanghai Shenkang Hospital Development Center SHDC2022CRT012
6 · The paper itself

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.

Indexed as

B7-H1 AntigenHistocompatibility Antigens Class IImmune Checkpoint InhibitorsLung NeoplasmsMembrane ProteinsProgrammed Cell Death 1 ReceptorRNA-Binding ProteinsSmall Cell Lung CarcinomaAnimalsBiomarkers, TumorCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMiceB7-H1 AntigenBiomarkers, TumorCD274 protein, humanHistocompatibility Antigens Class IIFITM3 protein, humanImmune Checkpoint InhibitorsMembrane ProteinsPDCD1 protein, humanProgrammed Cell Death 1 ReceptorRNA-Binding ProteinsIFITM3ImmunotherapyMHC-ISmall cell lung cancer

Identifiers

PMID40611157
PMCPMC12225533

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.