Laboratory of Applied Mechanobiology, Department for Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
Institute for Biology, Experimental Biophysics/Mechanobiology, Humboldt University of Berlin, Berlin, Germany.
Acta Biomater. 2021 Oct 1;133:222-230. doi: 10.1016/j.actbio.2021.02.026. Epub 2021 Feb 23.
Immunotherapy stands out as a powerful and promising therapeutic strategy in the treatment of cancer, infections, and autoimmune diseases. Adoptive immune therapies are usually centered on modified T cells and their specific expansion towards antigen-specific T cells against cancer and other diseases. However, despite their unmatched features, the potential of B cells in immunotherapy is just beginning to be explored. The main role of B cells in the immune response is to secrete antigen-specific antibodies and provide long-term protection against foreign pathogens. They further function as antigen-presenting cells (APCs) and secrete pro- and anti-inflammatory cytokines and thus exert positive and negative regulatory stimuli on other cells involved in the immune response such as T cells. Therefore, while hyperactivation of B cells can cause autoimmunity, their dysfunctions lead to severe immunodeficiencies. Only suitably activated B cells can play an active role in the treatment of cancers, infections, and autoimmune diseases. As a result, studies have focused on B cell-targeted immunotherapies in recent years. For this, the development, functions, interactions with the microenvironment, and clinical importance of B cells should be well understood. In this review, we summarize the main events during B cell activation. From the viewpoint of mechanobiology we discuss the translation of external cues such as surface topology, substrate stiffness, and biochemical signaling into B cell functions. We further dive into current B cell-targeted therapy strategies and their clinical applications. STATEMENT OF SIGNIFICANCE: B cells are proving as a promising tool in the field of immunotherapy. B cells exhibit various functions such as antibody production, antigen presentation or secretion of immune-regulatory factors which can be utilized in the fight against oncological or immunological disorders. In this review we discuss the importance of external mechanobiological cues such as surface topology, substrate stiffness, and biochemical signaling on B cell function. We further summarize B cell-targeted therapy strategies and their clinical applications, as in the context of anti-tumor responses and autoimmune diseases.
免疫疗法在癌症、感染和自身免疫性疾病的治疗中是一种强大且有前景的治疗策略。过继性免疫疗法通常以修饰后的 T 细胞为中心，并针对癌症和其他疾病的抗原特异性 T 细胞进行特异性扩增。然而，尽管 T 细胞具有无与伦比的特性，但 B 细胞在免疫疗法中的潜力才刚刚开始被探索。B 细胞在免疫反应中的主要作用是分泌抗原特异性抗体，并为对抗外来病原体提供长期保护。它们进一步作为抗原呈递细胞 (APC) 发挥作用，分泌促炎和抗炎细胞因子，从而对参与免疫反应的其他细胞（如 T 细胞）产生正向和负向调节刺激。因此，虽然 B 细胞的过度激活会导致自身免疫，但它们的功能障碍会导致严重的免疫缺陷。只有适当激活的 B 细胞才能在癌症、感染和自身免疫性疾病的治疗中发挥积极作用。因此，近年来研究集中在针对 B 细胞的免疫疗法上。为此，应该充分了解 B 细胞的发育、功能、与微环境的相互作用以及临床重要性。在这篇综述中，我们总结了 B 细胞激活过程中的主要事件。从力学生物学的角度出发，我们讨论了表面拓扑、基质硬度和生化信号等外部线索如何转化为 B 细胞的功能。我们进一步深入探讨了当前针对 B 细胞的治疗策略及其临床应用。
B 细胞在免疫疗法领域正被证明是一种很有前途的工具。B 细胞表现出多种功能，如产生抗体、抗原呈递或分泌免疫调节因子，这些功能可用于对抗肿瘤或免疫性疾病。在这篇综述中，我们讨论了表面拓扑、基质硬度和生化信号等外部力学生物学线索对 B 细胞功能的重要性。我们进一步总结了针对 B 细胞的治疗策略及其临床应用，包括在抗肿瘤反应和自身免疫性疾病中的应用。
