Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States.
Case Comprehensive Cancer Center, Cleveland, OH, United States.
Front Immunol. 2018 Feb 26;9:341. doi: 10.3389/fimmu.2018.00341. eCollection 2018.
Immunotherapy is revolutionizing cancer treatment. Recent clinical success with immune checkpoint inhibitors, chimeric antigen receptor T-cell therapy, and adoptive immune cellular therapies has generated excitement and new hopes for patients and investigators. However, clinically efficacious responses to cancer immunotherapy occur only in a minority of patients. One reason is the tumor microenvironment (TME), which potently inhibits the generation and delivery of optimal antitumor immune responses. As our understanding of TME continues to grow, strategies are being developed to change the TME toward one that augments the emergence of strong antitumor immunity. These strategies include eliminating tumor bulk to provoke the release of tumor antigens, using adjuvants to enhance antigen-presenting cell function, and employ agents that enhance immune cell effector activity. This article reviews the development of β-glucan and β-glucan-based nanoparticles as immune modulators of TME, as well as their potential benefit and future therapeutic applications. Cell-wall β-glucans from natural sources including plant, fungi, and bacteria are molecules that adopt pathogen-associated molecular pattern (PAMP) known to target specific receptors on immune cell subsets. Emerging data suggest that the TME can be actively manipulated by β-glucans and their related nanoparticles. In this review, we discuss the mechanisms of conditioning TME using β-glucan and β-glucan-based nanoparticles, and how this strategy enables future design of optimal combination cancer immunotherapies.
免疫疗法正在彻底改变癌症治疗。最近，免疫检查点抑制剂、嵌合抗原受体 T 细胞疗法和过继免疫细胞疗法的临床成功为患者和研究人员带来了兴奋和新的希望。然而，癌症免疫疗法的临床有效反应仅在少数患者中发生。原因之一是肿瘤微环境 (TME)，它强烈抑制了最佳抗肿瘤免疫反应的产生和传递。随着我们对 TME 的理解不断深入，正在开发策略来改变 TME，使其增强抗肿瘤免疫的出现。这些策略包括消除肿瘤体积以引发肿瘤抗原的释放，使用佐剂增强抗原呈递细胞的功能，并使用增强免疫细胞效应器活性的药物。本文综述了β-葡聚糖及其基于纳米颗粒作为 TME 免疫调节剂的发展，以及它们的潜在益处和未来的治疗应用。来自天然来源（包括植物、真菌和细菌）的细胞壁β-葡聚糖是一种已知能够靶向免疫细胞亚群特定受体的病原体相关分子模式 (PAMP) 分子。新出现的数据表明，TME 可以通过β-葡聚糖及其相关纳米颗粒进行主动调节。在这篇综述中，我们讨论了使用β-葡聚糖和基于β-葡聚糖的纳米颗粒调节 TME 的机制，以及这种策略如何能够为未来设计最佳组合癌症免疫疗法提供支持。
