Evidence map›Paper›PMID 38528526›Full record

ArticleMolecular cancer2024

rs822336 binding to C/EBPβ and NFIC modulates induction of PD-L1 expression and predicts anti-PD-1/PD-L1 therapy in advanced NSCLC.

Giovanna Polcaro, Luigi Liguori, Valentina Manzo, Annalisa Chianese, Giuliana Donadio, Alessandro Caputo, Giosuè Scognamiglio, Federica Dell'Annunziata, Maddalena Langella, Graziamaria Corbi and 14 more

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
6.8field-weighted citation impact, top 2% of its field
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

21 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. PD-L1/Cancers · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025
    Review
  9. Review
  10. Regulatory polymorphisms ofJournal for immunotherapy of cancer · 2025
    Article
  11. Review
  12. Clinical Relevance ofInternational journal of molecular sciences · 2025
    Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. The peripheral CD4Translational cancer research · 2024
    Article
  18. Review
  19. Review
  20. Observational
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

24 authors at 5 institutions in 1 country.

Giovanna Polcaro *Oncology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
Luigi Liguori *Oncology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
Valentina ManzoClinical Pharmacology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
Annalisa ChianeseDepartment of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, 80138, Italy.
Giuliana DonadioDepartment of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
Alessandro CaputoUniversity Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, 84131, Italy.
Giosuè ScognamiglioPathology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, 80131, Italy.
Federica Dell'AnnunziataDepartment of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, 80138, Italy.
Maddalena LangellaHematology and Transplant Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, 84131, Italy.
Graziamaria CorbiDepartment of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
Alessandro OttaianoDivision of Innovative Therapies for Abdominal Metastases, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, 80131, Italy.
Marco CascellaUnit of Anesthesiology, Intensive Care Medicine, and Pain Medicine, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
Francesco PerriMedical and Experimental Head and Neck Oncology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, 80131, Italy.
Margot De MarcoDepartment of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
Jessica Dal ColDepartment of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
Giovanni NassaLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
Giorgio GiuratoLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
Pio ZeppaUniversity Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, 84131, Italy.
Amelia FilippelliClinical Pharmacology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
Gianluigi FranciUniversity Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, 84131, Italy.
Fabrizio Dal PiazUniversity Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, 84131, Italy.
Valeria ContiClinical Pharmacology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy. vconti@unisa.it.
Stefano PepeOncology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy. spepe@unisa.it.
Francesco SabbatinoOncology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy. fsabbatino@unisa.it.
University of Salerno · ITOspedali Riuniti San Giovanni di Dio e Ruggi d'Aragona · ITIstituto Nazionale Tumori IRCCS "Fondazione G. Pascale" · ITUniversity of Campania "Luigi Vanvitelli" · ITUniversity of Naples Federico II · IT

Funding

PRIN 2017-COD. 2017PHRC8X_003
6 · The paper itself

Abstract

Efficient predictive biomarkers are needed for immune checkpoint inhibitor (ICI)-based immunotherapy in non-small cell lung cancer (NSCLC). Testing the predictive value of single nucleotide polymorphisms (SNPs) in programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has shown contrasting results. Here, we aim to validate the predictive value of PD-L1 SNPs in advanced NSCLC patients treated with ICIs as well as to define the molecular mechanisms underlying the role of the identified SNP candidate. rs822336 efficiently predicted response to anti-PD-1/PD-L1 immunotherapy in advanced non-oncogene addicted NSCLC patients as compared to rs2282055 and rs4143815. rs822336 mapped to the promoter/enhancer region of PD-L1, differentially affecting the induction of PD-L1 expression in human NSCLC cell lines as well as their susceptibility to HLA class I antigen matched PBMCs incubated with anti-PD-1 monoclonal antibody nivolumab. The induction of PD-L1 expression by rs822336 was mediated by a competitive allele-specificity binding of two identified transcription factors: C/EBPβ and NFIC. As a result, silencing of C/EBPβ and NFIC differentially regulated the induction of PD-L1 expression in human NSCLC cell lines carrying different rs822336 genotypes. Analysis by binding microarray further validated the competitive allele-specificity binding of C/EBPβ and NFIC to PD-L1 promoter/enhancer region based on rs822336 genotype in human NSCLC cell lines. These findings have high clinical relevance since identify rs822336 and induction of PD-L1 expression as novel biomarkers for predicting anti-PD-1/PD-L1-based immunotherapy in advanced NSCLC patients.

Indexed as

B7-H1 AntigenCarcinoma, Non-Small-Cell LungLung NeoplasmsBiomarkersCCAAT-Enhancer-Binding Protein-betaHumansImmune Checkpoint InhibitorsNFI Transcription FactorsB7-H1 AntigenBiomarkersCCAAT-Enhancer-Binding Protein-betaCEBPB protein, humanImmune Checkpoint InhibitorsNFIC protein, humanNFI Transcription FactorsImmunotherapyNSCLCPD-1PD-L1Predictive biomarkerrs822336SNP

Identifiers

PMID38528526
PMCPMC10962156
OpenAlexW4393155575

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.