dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Pinato, David J. |
dc.contributor.author | Murray, Sam M |
dc.contributor.author | Forner, Alejandro |
dc.contributor.author | Kaneko, Takahiro |
dc.contributor.author | Fessas, Petros |
dc.contributor.author | Toniutto, Pierluigi |
dc.contributor.author | Minguez Rosique, Beatriz |
dc.date.accessioned | 2022-05-02T13:16:26Z |
dc.date.available | 2022-05-02T13:16:26Z |
dc.date.issued | 2021-09-30 |
dc.identifier.citation | Pinato 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.issn | 2051-1426 |
dc.identifier.uri | https://hdl.handle.net/11351/7455 |
dc.description | Immunotherapy; Liver neoplasms |
dc.description.abstract | Background 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.iso | eng |
dc.publisher | BMJ |
dc.relation.ispartofseries | Journal for ImmunoTherapy of Cancer;9(9) |
dc.rights | Attribution-NonCommercial 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ |
dc.source | Scientia |
dc.subject | Fetge - Càncer - Tractament |
dc.subject | Hemostàtics |
dc.subject | Mort cel·lular |
dc.subject.mesh | Chemoembolization, Therapeutic |
dc.subject.mesh | Carcinoma, Hepatocellular |
dc.subject.mesh | /drug therapy |
dc.title | Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1136/jitc-2021-003311 |
dc.subject.decs | quimioembolización terapéutica |
dc.subject.decs | carcinoma hepatocelular |
dc.subject.decs | /farmacoterapia |
dc.relation.publishversion | http://dx.doi.org/10.1136/jitc-2021-003311 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut 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.pmid | 34593621 |
dc.identifier.wos | 000703191800004 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |