Show simple item record

 
dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorPinato, David J.
dc.contributor.authorMurray, Sam M
dc.contributor.authorForner, Alejandro
dc.contributor.authorKaneko, Takahiro
dc.contributor.authorFessas, Petros
dc.contributor.authorToniutto, Pierluigi
dc.contributor.authorMinguez Rosique, Beatriz
dc.date.accessioned2022-05-02T13:16:26Z
dc.date.available2022-05-02T13:16:26Z
dc.date.issued2021-09-30
dc.identifier.citationPinato DJ, Murray SM, Forner A, Kaneko T, Fessas P, Toniutto P, et al. Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy. J Immunother Cancer. 2021 Sep 30;9(9):e003311.
dc.identifier.issn2051-1426
dc.identifier.urihttp://hdl.handle.net/11351/7455
dc.descriptionImmunotherapy; Liver neoplasms
dc.description.abstractBackground Modulation of adaptive immunity may underscore the efficacy of trans-arterial chemoembolization (TACE). We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment. Methods We profiled intratumoral (IT), peritumoral (PT) and non-tumoral (NT) background tissue to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD-1+ T-cells across T+ (n=58) and T− (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, indoleamine 2,3 dehydrogenase (IDO-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), Lag-3, Tim-3 and CD163. Results We analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) hepatocellular carcinoma. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD-1+ and NT CD8+/PD-1+ (p<0.001) compared with T−. Lower IT (p=0.005) and NT CD4+/FOXP3+ (p=0.03) predicted for improved recurrence-free survival. In a subset of samples (n=24), transcriptomic analysis revealed upregulation of a pro-inflammatory response in T+. T+ samples were enriched for IRF2 expression (p=0.01), an interferon-regulated transcription factor implicated in cancer immune-evasion. T-cell clonality and expression of PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163 was similar in T+ versus T−. Conclusions TACE is associated with lower IT density of immune-exhausted effector cytotoxic and T-regs, with significant upregulation of pro-inflammatory pathways. This highlights the pleiotropic effects of TACE in modulating the tumor microenvironment and strengthens the rationale for developing immunotherapy alongside TACE.
dc.language.isoeng
dc.publisherBMJ
dc.relation.ispartofseriesJournal for ImmunoTherapy of Cancer;9(9)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectFetge - Càncer - Tractament
dc.subjectHemostàtics
dc.subjectMort cel·lular
dc.subject.meshChemoembolization, Therapeutic
dc.subject.meshCarcinoma, Hepatocellular
dc.subject.mesh/drug therapy
dc.titleTrans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1136/jitc-2021-003311
dc.subject.decsquimioembolización terapéutica
dc.subject.decscarcinoma hepatocelular
dc.subject.decs/farmacoterapia
dc.relation.publishversionhttp://dx.doi.org/10.1136/jitc-2021-003311
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Pinato DJ] Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK. Division of Oncology, Department of Translational Medicine, Universita del Piemonte Orientale "A. Avogadro", Novara, Italy. [Murray SM] Department of Infectious Diseases, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK. [Forner A] Liver Unit, Barcelona Clinic Liver Cancer (BCLC) Group, University of Barcelona, Hospital Clinic, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. [Kaneko T] Tokyo Medical and Dental University, Bunkyo-ku, Japan. [Fessas P] Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK. [Toniutto P] Hepatology and Liver Transplantation Unit, Department of Medical Area (DAME), University of Udine, Udine, Italy. [Mínguez B] Unitat del Fetge, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain
dc.identifier.pmid34593621
dc.identifier.wos000703191800004
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record