Laboratory of Experimental Hematology, Faculty of Medicine and Health Sciences, Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
Center for Oncological Research Antwerp, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Front Immunol. 2018 Mar 1;9:394. doi: 10.3389/fimmu.2018.00394. eCollection 2018.
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.
二十年的临床癌症研究表明，基于树突状细胞（DC）的疫苗接种是安全的，并且有提高存活率的能力，但单药治疗不太可能治愈癌症。这种个性化医疗旨在增强患者的抗肿瘤免疫力，因此，人们正在投入大量的研究努力来提高下一代 DC 疫苗的疗效，并寻找与现有癌症疗法的协同组合。免疫检查点方法旨在突破免疫抑制和逃逸，以加强抗肿瘤免疫，这在免疫治疗领域是一个启示。阻断程序性死亡-1（PD-1）途径的治疗性抗体的早期成功激发了新型抑制剂和联合疗法的开发。因此，将免疫调节肿瘤特异性 DC 策略与 PD-1 靶向方法相结合是一种很有前途的探索途径。在这篇综述中，我们重点关注 PD-1 信号在 DC 介导的抗肿瘤免疫中的作用。在探索 DC 疗法的全部潜力的过程中，我们讨论了通过阻止 PD-1 介导的免疫调节来利用 DC 免疫原性的不同策略，包括针对治疗性抗体的最先进研究、化疗诱导的免疫激活的经验教训，以及最近在可溶性分子和基因沉默技术方面的发展。目前正在进行临床前和临床研究的 DC/PD-1 免疫治疗组合概述了这种联合策略的临床潜力。
