Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (IMEX)-CONICET-Academia Nacional de Medicina (ANM), Buenos Aires, Argentina.
Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Leuk Lymphoma. 2020 Oct;61(10):2409-2418. doi: 10.1080/10428194.2020.1753043. Epub 2020 Apr 19.
Ibrutinib is a BTK/ITK inhibitor with efficacy for the treatment of various lymphoid cancers, including CLL. Considering that innate and adaptative immune defects are a dominant feature of CLL patients, we evaluated whether ibrutinib affects the survival and function of neutrophils and γδ T cells, key players of the early immune response against microbes. Neutrophils and γδ T cells were obtained from peripheral blood of healthy donors and CLL patients. We found that ibrutinib reduces the production of reactive oxygen species (ROS) and bacteria killing capacity, and slightly impairs neutrophil extracellular traps (NETs) production without affecting bacteria-uptake and CD62L-downregulation induced by fMLP or aggregated IgG. In addition, ibrutinib reduces γδ T cell activation and CD107a degranulation induced by phosphoantigens or anti-CD3. These findings are in agreement with previous data suggesting that ibrutinib interferes with the protective immune response to pathogens, particularly Mycobacteria and .
伊布替尼是一种 BTK/ITK 抑制剂，具有治疗各种淋巴癌的功效，包括 CLL。鉴于 CLL 患者存在固有和适应性免疫缺陷，我们评估了伊布替尼是否会影响中性粒细胞和 γδ T 细胞（微生物早期免疫反应的关键参与者）的存活和功能。我们从健康供体和 CLL 患者的外周血中获得中性粒细胞和 γδ T 细胞。我们发现伊布替尼可降低活性氧物质 (ROS) 的产生和杀菌能力，并轻微损害中性粒细胞胞外诱捕网 (NETs) 的产生，而不会影响 fMLP 或聚集 IgG 诱导的细菌摄取和 CD62L 下调。此外，伊布替尼可降低磷酸抗原或抗 CD3 诱导的 γδ T 细胞活化和 CD107a 脱颗粒。这些发现与先前的数据一致，表明伊布替尼会干扰对病原体的保护性免疫反应，尤其是分枝杆菌和。
