Human NK cells: from surface receptors to the therapy of leukemias and solid tumors.
Human NK cells: from surface receptors to the therapy of leukemias and solid tumors.
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DOI：
10.3389/fimmu.2014.00087
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发表时间：
2014
影响因子：
7.3
通讯作者：
Mingari MC
中科院分区：
文献类型：
--
作者：
Moretta L;Pietra G;Montaldo E;Vacca P;Pende D;Falco M;Del Zotto G;Locatelli F;Moretta A;Mingari MC
自然杀伤细胞（NK）是先天免疫的主要效应细胞。二十多年前，主要组织相容性复合体i类特异性抑制性NK受体的发现，以及随后的激活受体，识别肿瘤或病毒感染细胞表达的配体，为我们理解选择性识别和杀死肿瘤细胞的机制铺平了道路。尽管NK细胞在体外可以有效地杀死不同组织型的肿瘤细胞，但在体内，NK细胞的活性可能受到肿瘤细胞自身和肿瘤微环境对其功能的抑制而受到限制。另一方面，NK细胞在单倍体造血干细胞（HSC）移植治疗高危白血病中的重要作用已被清楚地证明。来源于供体造血干细胞的NK细胞杀死调理方案后残留的白血病细胞，从而防止白血病复发。此外，它们还能杀死残留的树突状细胞和T淋巴细胞，从而预防GvH疾病和移植物排斥反应。
Natural Killer (NK) cells are major effector cells of the innate immunity. The discovery, over two decades ago, of major histocompatibility complex-class I-specific inhibitory NK receptors and subsequently of activating receptors, recognizing ligands expressed by tumor or virus-infected cells, paved the way to our understanding of the mechanisms of selective recognition and killing of tumor cells. Although NK cells can efficiently kill tumor cells of different histotypes in vitro, their activity may be limited in vivo by their inefficient trafficking to tumor lesions and by the inhibition of their function induced by tumor cells themselves and by the tumor microenvironment. On the other hand, the important role of NK cells has been clearly demonstrated in the therapy of high risk leukemias in the haploidentical hematopoietic stem cell (HSC) transplantation setting. NK cells derived from donor HSC kill leukemic cells residual after the conditioning regimen, thus preventing leukemia relapses. In addition, they also kill residual dendritic cells and T lymphocytes, thus preventing both GvH disease and graft rejection.