Immunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain.
Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
Front Immunol. 2022 May 4;13:884648. doi: 10.3389/fimmu.2022.884648. eCollection 2022.
Natural killer (NK) cells are lymphocytes with a key role in the defense against viral infections and tumor cells. Although NK cells are classified as innate lymphoid cells (ILCs), under certain circumstances they exhibit adaptive and memory-like features. The latter may be achieved, among others, by a brief stimulation with interleukin (IL)-12, IL-15 and IL-18. These cytokine-induced memory-like (CIML) NK cells resemble the trained immunity observed in myeloid cells. CIML NK cells undergo transcriptional, epigenetic and metabolic reprogramming that, along with changes in the expression of cell surface receptors and components of cytotoxic granules, are responsible for their enhanced effector functions after a resting period. In addition, these memory-like NK cells persist for a long time, which make them a good candidate for cancer immunotherapy. Currently, several clinical trials are testing CIML NK cells infusions to treat tumors, mostly hematological malignancies. In relapse/refractory acute myeloid leukemia (AML), the adoptive transfer of CIML NK cells is safe and complete clinical remissions have been observed. In our review, we sought to summarize the current knowledge about the generation and molecular basis of NK cell memory-like responses and the up-to-date results from clinical trials with CIML NK cells.
自然杀伤 (NK) 细胞是具有关键作用的淋巴细胞，可防御病毒感染和肿瘤细胞。尽管 NK 细胞被归类为先天淋巴细胞 (ILC)，但在某些情况下，它们表现出适应性和记忆样特征。后者可以通过短暂刺激白细胞介素 (IL)-12、IL-15 和 IL-18 来实现。这些细胞因子诱导的记忆样 (CIML) NK 细胞类似于在髓样细胞中观察到的训练免疫。CIMLNK 细胞经历转录、表观遗传和代谢重编程，以及细胞表面受体和细胞毒性颗粒成分表达的变化，这使得它们在休息一段时间后增强了效应功能。此外，这些记忆样 NK 细胞可以长期存在，这使它们成为癌症免疫治疗的一个很好的候选者。目前，几项临床试验正在测试 CIMLNK 细胞输注以治疗肿瘤，主要是血液系统恶性肿瘤。在复发/难治性急性髓系白血病 (AML) 中，CIMLNK 细胞的过继转移是安全的，并且已经观察到完全临床缓解。在我们的综述中，我们试图总结关于 NK 细胞记忆样反应的产生和分子基础的最新知识，以及 CIMLNK 细胞临床试验的最新结果。
