Immunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain.
Biodonostia Health Research Institute, Hematology and Hemotherapy Service, Donostia University Hospital, Donostia-San Sebastián, Spain.
Front Immunol. 2021 Oct 5;12:748207. doi: 10.3389/fimmu.2021.748207. eCollection 2021.
Autologous hematopoietic stem cell transplantation (autoHSCT) is a standard of care for transplant-eligible patients with multiple myeloma (MM). Among factors that influence outcome after autoHSCT, it has been suggested that the number of natural killer (NK) cells plays an important role. However, the impact that different NK cell subsets and their phenotype could have in disease progression after autoHSCT are less clear. For this reason, we have phenotypically and functionally characterized NK cells during immune system reconstitution after autoHSCT in 54 MM patients. Shortly after leukocyte recovery, an extensive redistribution of NK cell subsets occurs in these patients. In addition, NK cells undergo a profound phenotypic change characterized, among others, by their increased proliferative capacity and immature phenotype. Importantly, MM patients who showed lower frequencies of the mature highly differentiated NKG2A-CD57+ NK cell subset at +30 and +100 days after autoHSCT experienced superior progression-free survival and had a longer time to the next treatment than those with higher frequencies. Our results provide significant insights into NK cell reconstitution after autoHSCT and suggest that the degree of NK cell maturation after autoHSCT affects the clinical outcome of MM patients treated with this therapeutic strategy.
自体造血干细胞移植（autoHSCT）是适合移植的多发性骨髓瘤（MM）患者的标准治疗方法。在影响 autoHSCT 后结果的因素中，有人认为自然杀伤（NK）细胞的数量起着重要作用。然而，不同 NK 细胞亚群及其表型在 autoHSCT 后疾病进展中的影响尚不清楚。出于这个原因，我们在 54 名 MM 患者的 autoHSCT 后免疫系统重建期间对 NK 细胞进行了表型和功能特征分析。在白细胞恢复后不久，这些患者的 NK 细胞亚群发生了广泛的重新分布。此外，NK 细胞经历了深刻的表型变化，其特征是增殖能力增加和不成熟表型。重要的是，在 autoHSCT 后 30 天和 100 天，NK 细胞中成熟的高度分化的 NKG2A-CD57+NK 细胞亚群频率较低的 MM 患者的无进展生存期更好，并且与那些频率较高的患者相比，下一阶段治疗的时间更长。我们的研究结果为 autoHSCT 后 NK 细胞重建提供了重要的见解，并表明 autoHSCT 后 NK 细胞成熟程度会影响接受这种治疗策略的 MM 患者的临床结局。
