Bruton’s tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a pivotal role in B cell biology and function. As an essential component of the B cell receptor (BCR) signaling pathway, BTK is expressed not only in B cells but also in myeloid cells, including monocytes/macrophages, dendritic cells, neutrophils, and mast cells. BTK inhibitors (BTKis) have revolutionized the treatment of chronic lymphocytic leukemia (CLL) and other B cell malignancies. Besides their well-characterized role in inhibiting BCR signaling, BTKis also exert significant immunological influences outside the tumor cell that extend their therapeutic potential and impact on the immune system in different ways. This work elucidates the immunomodulatory mechanisms associated with BTK inhibition, focusing on CLL and other clinical contexts. We discuss how BTK inhibition affects various immune cells, including B cells, T cells, and macrophages. The effects of BTKis on the profiles of cytokines, also fundamental parts of the tumor microenvironment (TME), are summarized here as well. This review also appraises the implications of these immunomodulatory actions in the management of autoimmune diseases and infections. Summarizing the dual role of BTK inhibition in modulating malignant lymphocyte and immune cell functions, this paper highlights the broader potential clinical use of compounds targeting BTK.
布鲁顿酪氨酸激酶（BTK）是一种胞质酪氨酸激酶，在B细胞生物学及功能中发挥关键作用。作为B细胞受体（BCR）信号通路的核心组分，BTK不仅表达于B细胞，也存在于髓系细胞（包括单核细胞/巨噬细胞、树突状细胞、中性粒细胞和肥大细胞）中。BTK抑制剂（BTKis）已彻底改变了慢性淋巴细胞白血病（CLL）及其他B细胞恶性肿瘤的治疗格局。除了其明确的抑制BCR信号传导作用外，BTKis还能在肿瘤细胞外产生显著的免疫调节效应，通过不同方式拓展其治疗潜力并影响免疫系统。本文重点围绕CLL及其他临床背景，系统阐释了BTK抑制相关的免疫调节机制。我们探讨了BTK抑制如何影响B细胞、T细胞和巨噬细胞等多种免疫细胞的功能，并总结了BTKis对肿瘤微环境（TME）关键组分——细胞因子谱系的影响。本综述还评估了这些免疫调节作用在自身免疫性疾病及感染管理中的临床意义。通过总结BTK抑制在调控恶性淋巴细胞与免疫细胞功能中的双重作用，本文揭示了靶向BTK化合物更广阔的潜在临床应用前景。
The Immunomodulatory Mechanisms of BTK Inhibition in CLL and Beyond
肿瘤(癌症)患者之家