AUTHOR=Versteven Maarten , Van den Bergh Johan M. J. , Marcq Elly , Smits Evelien L. J. , Van Tendeloo Viggo F. I. , Hobo Willemijn , Lion Eva 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00394

DOI=10.3389/fimmu.2018.00394

ISSN=1664-3224

ABSTRACT=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.