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Front Immunol. 2018 Mar 1;9:394. doi: 10.3389/fimmu.2018.00394. eCollection 2018.

Dendritic Cells and Programmed Death-1 Blockade: A Joint Venture to Combat Cancer.

Author information

1
Laboratory of Experimental Hematology, Faculty of Medicine and Health Sciences, Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
2
Center for Oncological Research Antwerp, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
3
Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium.
4
Laboratory of Hematology, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.

Abstract

Two decades of clinical cancer research with dendritic cell (DC)-based vaccination have proved that this type of personalized medicine is safe and has the capacity to improve survival, but monotherapy is unlikely to cure the cancer. Designed to empower the patient's antitumor immunity, huge research efforts are set to improve the efficacy of next-generation DC vaccines and to find synergistic combinations with existing cancer therapies. Immune checkpoint approaches, aiming to breach immune suppression and evasion to reinforce antitumor immunity, have been a revelation in the immunotherapy field. Early success of therapeutic antibodies blocking the programmed death-1 (PD-1) pathway has sparked the development of novel inhibitors and combination therapies. Hence, merging immunoregulatory tumor-specific DC strategies with PD-1-targeted approaches is a promising path to explore. In this review, we focus on the role of PD-1-signaling in DC-mediated antitumor immunity. In the quest of exploiting the full potential of DC therapy, different strategies to leverage DC immunopotency by impeding PD-1-mediated immune regulation are discussed, including the most advanced research on targeted therapeutic antibodies, lessons learned from chemotherapy-induced immune activation, and more recent developments with soluble molecules and gene-silencing techniques. An overview of DC/PD-1 immunotherapy combinations that are currently under preclinical and clinical investigation substantiates the clinical potential of such combination strategies.

KEYWORDS:

cancer immunotherapy; combination therapy; dendritic cell; programmed death ligand 1/2; programmed death-1

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