期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.00394
关键词
dendritic cell; programmed death-1; cancer immunotherapy; combination therapy; programmed death ligand 1/2
类别
资金
- University of Antwerp (Special Research Fund, BOF-KP Project) [32809]
- Stichting tegen Kanker (Belgian Foundation against Cancer) [2014-155]
- Kom op tegen Kanker (Stand up to Cancer-the Flemish Cancer Society)
- SB-fellowship from the Research Foundation-Flanders (FWO) [1S24517N]
- Emmanuel van der Schueren fellowship from Kom op tegen Kanker
- Flanders Innovation & Entrepreneurship (IWT) [141433]
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.
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