Amelioration of NK cell function driven by Vα24+ invariant NKT cell activation in multiple myeloma
Amelioration of NK cell function driven by Vα24+ invariant NKT cell activation in multiple myeloma
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DOI：
10.1016/j.clim.2017.10.007
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发表时间：
2018-02-01
影响因子：
8.6
通讯作者：
Fujii, Shin-ichiro
中科院分区：
文献类型：
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作者：
Iyoda, Tomonori;Yamasaki, Satoru;Fujii, Shin-ichiro
NK细胞是免疫防御的第一道防线，但在多发性骨髓瘤（MM）患者中逐渐失调。为了恢复和促进其抗肿瘤作用，需要足够数量的NK细胞，并且必须刺激NK细胞。我们初步评估了34例MM患者的NKT和NK细胞比例。两者在PBMC群体中的频率均与BMMNC中的频率相关，而与低BMMNC数量无关。然后，我们评估了用CD 1d和α-GalCer复合物刺激NKT细胞对NK细胞的抑制作用。NKT细胞活化后，CDS 6（dim）CD 16（+）NK细胞上NKG 2D和CD 56（bright）CD 16（-）NK细胞上DNAM-1的表达增加。显然是的NK细胞介导的抗肿瘤作用依赖于骨髓瘤细胞上的NKG 2D和DNAM-1配体。因此，患者的NK细胞功能可以通过NKT细胞活化而改善，超出免疫抑制的效果。这种NKT驱动的NK细胞疗法可能代表一种潜在的新治疗方式。(C)2017爱思唯尔公司All rights reserved.
NK cells represent a first line of immune defense, but are progressively dysregulated in multiple myeloma (MM) patients. To restore and facilitate their antitumor effect, NK cells are required in sufficient quantities and must be stimulated. We initially assessed the proportions of NKT and NK cells in 34 MM patients. The frequencies of both in PBMC populations correlated with those in BMMNCs irrespective of low BMMNC numbers. We then assessed the adjunctive effect of stimulating NKT cells with CD1d and alpha-GalCer complexes on the NK cells. The expression of NKG2D on CDS6(dim)CD16(+) NK cells and DNAM-1 on CD56(bright)CD16(-) NK cells increased after NKT cell activation. Apparently. NK cell-mediated anti-tumor effects were dependent on NKG2D and DNAM-1 ligands on myeloma cells. Thus, NK cell function in patients could be ameliorated, beyond the effect of immunosuppression, by NKT cell activation. This NKT-driven NK cell therapy could represent a potential new treatment modality. (C) 2017 Elsevier Inc. All rights reserved.