|Title:||Harnessing immunotherapy for liver recipients with hepatocellular carcinoma: a review from a transplant oncology perspective||Authors:||CHENG-MAW HO
|Issue Date:||2019||Publisher:||SAGE Publications Inc.||Journal Volume:||11||Source:||Therapeutic Advances in Medical Oncology||Abstract:||
Without stringent criteria, liver transplantation for hepatocellular carcinoma (HCC) can lead to high cancer recurrence and poor prognosis in the current treatment context. Checkpoint inhibitors can lead to long survival by targeting coinhibitory pathways and promoting T-cell activity; thus, they have great potential for cancer immunotherapy. Therapeutic modulation of cosignaling pathways may shift paradigms from surgical prevention of recurrence to oncological intervention. Herein, we review the available evidence from a therapeutic perspective and focus on immune microenvironment perturbation by immunosuppressants and checkpoint inhibitors. Partial and reversible interleukin-2 signaling blockade is the mainstream strategy of immunosuppression for graft protection. Programmed cell death protein 1 (PD-1) is abundantly expressed on human liver allograft-infiltrating T-cells, which proliferate considerably after programmed death-ligand 1 (PD-L1) blockade. Clinically, checkpoint inhibitors are used in heart, liver, and kidney recipients with various cancers. Rejection can occur after checkpoint inhibitor administration through acute T-cell-mediated, antibody-mediated, or chronic allograft rejection mechanisms. Nevertheless, liver recipients may demonstrate favorable responses to treatment for HCC recurrence without rejection. Pharmacodynamically, substantial degrees of receptor occupancy can be achieved with lower doses, with favorable clinical outcomes. Manipulation of the immune microenvironment is a therapeutic niche that balances seemingly conflicting anticancer and graft protection needs. Additional translational and clinical studies emphasizing the comparative effectiveness of signaling networks within the immune microenvironment and conducting overall assessment of the immune microenvironment may aid in creating a therapeutic window and benefiting future liver recipients with HCC recurrence. ? The Author(s), 2019.
|ISSN:||1758-8340||DOI:||10.1177/1758835919843463||SDG/Keyword:||antineoplastic monoclonal antibody; calcineurin; calcineurin inhibitor; CD20 antibody; cytokeratin 7; cytokeratin 9; cytotoxic T lymphocyte antigen 4; dendritic cell vaccine; everolimus; hepatitis A virus cellular receptor 2; I kappa B; immunosuppressive agent; interleukin 2; mitogen activated protein kinase; nivolumab; pembrolizumab; programmed death 1 ligand 1; programmed death 1 ligand 1 inhibitor; programmed death 1 receptor; programmed death 1 receptor inhibitor; rapamycin; Ras protein; T lymphocyte receptor; unclassified drug; add on therapy; antineoplastic activity; cancer immunization; cancer immunotherapy; cancer inhibition; cancer recurrence; cell therapy; chimeric antigen receptor T-cell immunotherapy; clinical outcome; drug efficacy; drug targeting; graft recipient; human; immune response; immunomodulation; intestine flora; liver cell carcinoma; liver graft rejection; liver transplantation; MAPK signaling; nonhuman; overall survival; priority journal; Review; signal transduction; T lymphocyte activation; transplantation conditioning; treatment response; virus load
|Appears in Collections:||醫學系|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.