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首页> 美国卫生研究院文献>other >Novel Strategy to Expand Super-Charged NK Cells with Significant Potential to Lyse and Differentiate Cancer Stem Cells: Differences in NK Expansion and Function between Healthy and Cancer Patients
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Novel Strategy to Expand Super-Charged NK Cells with Significant Potential to Lyse and Differentiate Cancer Stem Cells: Differences in NK Expansion and Function between Healthy and Cancer Patients

机译：一种新的战略以扩大具有充电能力和分化癌症干细胞的潜力的超负荷NK细胞：健康和癌症患者之间NK扩展和功能的差异

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摘要

Natural killer (NK) cells are known to target cancer stem cells and undifferentiated tumors. In this paper, we provide a novel strategy for expanding large numbers of super-charged NK cells with significant potential to lyse and differentiate cancer stem cells and demonstrate the differences in the dynamics of NK cell expansion between healthy donors and cancer patients. Decline in cytotoxicity and lower interferon (IFN)-γ secretion by osteoclast (OC)-expanded NK cells from cancer patients correlates with faster expansion of residual contaminating T cells within purified NK cells, whereas healthy donors’ OCs continue expanding super-charged NK cells while limiting T cell expansion for up to 60 days. Similar to patient NK cells, NK cells from tumor-bearing BLT-humanized mice promote faster expansion of residual T cells resulting in decreased numbers and function of NK cells, whereas NK cells from mice with no tumor continue expanding NK cells and retain their cytotoxicity. In addition, dendritic cells (DCs) in contrast to OCs are found to promote faster expansion of residual T cells within purified NK cells resulting in the decline in NK cell numbers from healthy individuals. Addition of anti-CD3 mAb inhibits T cell proliferation while enhancing NK cell expansion; however, expanding NK cells have lower cytotoxicity but higher secretion of IFN-γ. Expansion and functional activation of super-charged NK cells by OCs is dependent on interleukin (IL)-12 and IL-15. Thus, in this report, we not only provide a novel strategy to expand super-charged NK cells, but also demonstrate that rapid and sustained expansion of residual T cells within the purified NK cells during expansion with DCs or OCs could be a potential mechanism by which the numbers and function of NK cells decline in cancer patients and in BLT-humanized mice.
机译：已知自然杀伤（NK）细胞靶向癌症干细胞和未分化的肿瘤。在本文中，我们提供了一种新的策略，可扩展具有大量潜力的超负荷NK细胞，以裂解和分化癌症干细胞，并证明健康供体和癌症患者之间NK细胞扩增动力学的差异。癌症患者破骨细胞（OC）扩增的NK细胞的细胞毒性下降和干扰素（IFN）-γ分泌降低与纯化的NK细胞内残留污染性T细胞的更快扩增有关，而健康供体的OC继续使超荷NK细胞扩增同时限制T细胞的扩展长达60天。与患者NK细胞相似，来自荷瘤BLT人源化小鼠的NK细胞促进残留T细胞的更快扩增，从而导致NK细胞数量和功能降低，而来自无肿瘤小鼠的NK细胞则继续扩展NK细胞并保留其细胞毒性。另外，发现与OC相反，树突状细胞（DC）促进纯化的NK细胞内残留T细胞的更快扩增，导致健康个体的NK细胞数量减少。抗CD3 mAb的添加可抑制T细胞增殖，同时增强NK细胞的扩增；然而，扩增的NK细胞具有较低的细胞毒性，但具有较高的IFN-γ分泌。 OCs对超负荷NK细胞的扩增和功能激活取决于白介素（IL）-12和IL-15。因此，在本报告中，我们不仅提供了一种扩展超荷NK细胞的新策略，而且还证明了在用DC或OC扩增过程中，纯化的NK细胞中残余T细胞的快速和持续扩增可能是一种潜在的机制。在癌症患者和BLT人源化小鼠中NK细胞的数量和功能下降。

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