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Front. Immunol. | doi: 10.3389/fimmu.2018.00394

Dendritic cells and programmed death-1 blockade: a joint venture to combat cancer

 Maarten Versteven1*,  Johan Van den Bergh1,  Elly Marcq2, Evelien Smits1, 2, 3,  Viggo Van Tendeloo1, Willemijn Hobo4 and  Eva Lion1, 3
  • 1Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Belgium
  • 2Centre for Oncological Research Antwerp, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium
  • 3Centre for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Belgium
  • 4Laboratory of Hematology, Department of Laboratory Medicine, Medical Center, Radboud University Nijmegen, Netherlands

Two decades of clinical cancer research with dendritic cell (DC)-based vaccination have learned us that this type of personalized medicine is safe and has the capacity to improve survival, but as a 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, substantiate the clinical potential of such combination strategies.

Keywords: Dendritic Cells, Programmed death-1, cancer immunotherapy, combination therapy, Programmed death ligand-1 and 2

Received: 15 Jan 2018; Accepted: 13 Feb 2018.

Edited by:

Piergiuseppe De Berardinis, Istituto di Biochimica delle Proteine (CNR), Italy

Reviewed by:

Dalil Hannani, UMR5525 Techniques de l'Ingénierie Médicale et de la Complexité Informatique, Mathématiques et Applications, Grenoble (TIMC-IMAG), France
Daniela Fenoglio, Università di Genova, Italy  

Copyright: © 2018 Versteven, Van den Bergh, Marcq, Smits, Van Tendeloo, Hobo and Lion. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mr. Maarten Versteven, University of Antwerp, Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, Antwerp, Belgium, maarten.versteven@uantwerpen.be