Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
Front Immunol. 2022 Aug 19;13:962552. doi: 10.3389/fimmu.2022.962552. eCollection 2022.
Chronic lymphocytic leukemia (CLL), a highly heterogeneous B-cell malignancy, is characterized by tumor microenvironment disorder and T-cell immune dysfunction, which play a major role in the proliferation and survival of CLL cells. Ibrutinib is the first irreversible inhibitor of Bruton's tyrosine kinase (BTK). In addition to targeting B-cell receptor (BCR) signaling to kill tumor cells, increasing evidence has suggested that ibrutinib regulates the tumor microenvironment and T-cell immunity in a direct and indirect manner. For example, ibrutinib not only reverses the tumor microenvironment by blocking cytokine networks and toll-like receptor signaling but also regulates T cells in number, subset distribution, T-cell receptor (TCR) repertoire and immune function by inhibiting interleukin-2 inducible T-cell kinase (ITK) and reducing the expression of inhibitory receptors, and so on. In this review, we summarize the current evidence for the effects of ibrutinib on the tumor microenvironment and cellular immunity of patients with CLL, particularly for the behavior and function of T cells, explore its potential mechanisms, and provide a basis for the clinical benefits of long-term ibrutinib treatment and combined therapy based on T-cell-based immunotherapies.
慢性淋巴细胞白血病（CLL）是一种高度异质性的 B 细胞恶性肿瘤，其特征是肿瘤微环境紊乱和 T 细胞免疫功能障碍，这在 CLL 细胞的增殖和存活中起着主要作用。伊布替尼是首个不可逆的布鲁顿酪氨酸激酶（BTK）抑制剂。除了通过靶向 B 细胞受体（BCR）信号来杀伤肿瘤细胞外，越来越多的证据表明伊布替尼通过直接和间接方式调节肿瘤微环境和 T 细胞免疫。例如，伊布替尼不仅通过阻断细胞因子网络和 Toll 样受体信号来逆转肿瘤微环境，而且通过抑制白细胞介素-2 可诱导的 T 细胞激酶（ITK）和减少抑制性受体的表达来调节 T 细胞的数量、亚群分布、T 细胞受体（TCR）谱和免疫功能等。在这篇综述中，我们总结了伊布替尼对 CLL 患者肿瘤微环境和细胞免疫的影响的现有证据，特别是对 T 细胞的行为和功能的影响，探讨了其潜在机制，并为长期伊布替尼治疗和基于 T 细胞的免疫疗法的联合治疗的临床获益提供了依据。
