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NK Cell Subgroups Phenotype and Functions After Autologous Stem Cell Transplantation

机译:自体干细胞移植后NK细胞亚组表型和功能。

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摘要

High-dose chemotherapy with consecutive autologous stem cell transplantation (autoSCT) is a well-established treatment option for patients suffering from malignant lymphoma or multiple myeloma. Natural killer (NK) cells are an important part of the immune surveillance, and their cell number after autoSCT is predictive for progression-free and overall survival. To improve knowledge about the role of NK cells after autoSCT, we investigated different NK cell subgroups, their phenotype, and their functions in patients treated with autoSCT. Directly after leukocyte regeneration (>1000 leukocytes/μl) following autoSCT, CD56++ NK cells were the major NK cell subset. Surprisingly, these cells showed unusually high surface expression levels of CD57 and killer Ig-like receptors (KIRs) compared to expression levels before or at later time points after autoSCT. Moreover, these NK cells strongly upregulated KIR2DL2/3/S2 and KIR3DL1, whereas KIR2DL1/S1 remained constant, indicating that this cell population arose from more immature NK cells instead of from activated mature ones. Remarkably, NK cells were already able to degranulate and produce IFN-γ and MIP-1β upon tumor interaction early after leukocyte regeneration. In conclusion, we describe an unusual upregulation of CD57 and KIRs on CD56++ NK cells shortly after autoSCT. Importantly, these NK cells were functionally competent upon tumor interaction at this early time point.
机译:大剂量化学疗法和连续自体干细胞移植(autoSCT)是恶性淋巴瘤或多发性骨髓瘤患者公认的治疗选择。天然杀伤(NK)细胞是免疫监测的重要组成部分,autoSCT后其细胞数量可预测无进展生存期和总生存期。为了提高对autoSCT后NK细胞作用的认识,我们调查了接受autoSCT治疗的患者中不同的NK细胞亚群,它们的表型和功能。 autoSCT后白细胞再生(> 1000白细胞/μl)后,CD56 ++ NK细胞是主要的NK细胞亚群。令人惊讶的是,与autoSCT之前或之后的时间点的表达水平相比,这些细胞显示出异常高的CD57和杀伤性Ig样受体(KIR)表面表达水平。此外,这些NK细胞强烈上调KIR2DL2 / 3 / S2和KIR3DL1,而KIR2DL1 / S1保持恒定,表明该细胞群是由更多未成熟的NK细胞而不是由活化的成熟细胞产生的。值得注意的是,在白细胞再生后的早期肿瘤相互作用时,NK细胞已经能够脱粒并产生IFN-γ和MIP-1β。总之,我们描述了autoSCT后不久,CD56 ++ NK细胞CD57和KIRs异常上调。重要的是,在此早期时间点,这些NK细胞在功能上与肿瘤相互作用有关。

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