Your browser doesn't support javascript.
loading
rs822336 binding to C/EBPß and NFIC modulates induction of PD-L1 expression and predicts anti-PD-1/PD-L1 therapy in advanced NSCLC.
Polcaro, Giovanna; Liguori, Luigi; Manzo, Valentina; Chianese, Annalisa; Donadio, Giuliana; Caputo, Alessandro; Scognamiglio, Giosuè; Dell'Annunziata, Federica; Langella, Maddalena; Corbi, Graziamaria; Ottaiano, Alessandro; Cascella, Marco; Perri, Francesco; De Marco, Margot; Col, Jessica Dal; Nassa, Giovanni; Giurato, Giorgio; Zeppa, Pio; Filippelli, Amelia; Franci, Gianluigi; Piaz, Fabrizio Dal; Conti, Valeria; Pepe, Stefano; Sabbatino, Francesco.
Afiliación
  • Polcaro G; Oncology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
  • Liguori L; Oncology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
  • Manzo V; Oncology Unit, Department of Medicine, Surgery and Dentistry, University of Naples "Federico II", Naples, 80131, Italy.
  • Chianese A; Clinical Pharmacology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
  • Donadio G; University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, 84131, Italy.
  • Caputo A; Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, 80138, Italy.
  • Scognamiglio G; Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
  • Dell'Annunziata F; University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, 84131, Italy.
  • Langella M; Pathology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
  • Corbi G; Pathology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, 80131, Italy.
  • Ottaiano A; Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, 80138, Italy.
  • Cascella M; Hematology and Transplant Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, 84131, Italy.
  • Perri F; Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
  • De Marco M; Division of Innovative Therapies for Abdominal Metastases, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, 80131, Italy.
  • Col JD; Unit of Anesthesiology, Intensive Care Medicine, and Pain Medicine, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
  • Nassa G; Medical and Experimental Head and Neck Oncology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, 80131, Italy.
  • Giurato G; Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
  • Zeppa P; Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
  • Filippelli A; Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
  • Franci G; Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
  • Piaz FD; University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, 84131, Italy.
  • Conti V; Pathology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
  • Pepe S; Clinical Pharmacology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081, Italy.
  • Sabbatino F; University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, 84131, Italy.
Mol Cancer ; 23(1): 63, 2024 03 25.
Article en En | MEDLINE | ID: mdl-38528526
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/EBPß and NFIC. As a result, silencing of C/EBPß 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/EBPß 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.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Antígeno B7-H1 / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Mol Cancer Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Antígeno B7-H1 / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Mol Cancer Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido