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Natural Killer Cells: Angels and Devils for Immunotherapy

机译:天然杀伤细胞:免疫疗法的天使和魔鬼

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摘要

In recent years, the relevance of the immune system to fight cancer has led to the development of immunotherapy, including the adoptive cell transfer of immune cells, such as natural killer (NK) cells and chimeric antigen receptors (CAR)-modified T cells. The discovery of donor NK cells’ anti-tumor activity in acute myeloid leukemia patients receiving allogeneic stem cell transplantation (allo-SCT) was the trigger to conduct many clinical trials infusing NK cells. Surprisingly, many of these studies did not obtain optimal results, suggesting that many different NK cell parameters combined with the best clinical protocol need to be optimized. Various parameters including the high array of activating receptors that NK cells have, the source of NK cells selected to treat patients, different cytotoxic mechanisms that NK cells activate depending on the target cell and tumor cell survival mechanisms need to be considered before choosing the best immunotherapeutic strategy using NK cells. In this review, we will discuss these parameters to help improve current strategies using NK cells in cancer therapy. Moreover, the chimeric antigen receptor (CAR) modification, which has revolutionized the concept of immunotherapy, will be discussed in the context of NK cells. Lastly, the dark side of NK cells and their involvement in inflammation will also be discussed.
机译:近年来,免疫系统与癌症作斗争的重要性已导致免疫疗法的发展,包括免疫细胞的过继细胞转移,例如自然杀伤(NK)细胞和嵌合抗原受体(CAR)修饰的T细胞。在接受同种异体干细胞移植(allo-SCT)的急性髓细胞性白血病患者中发现供体NK细胞的抗肿瘤活性,是进行许多注入NK细胞临床试验的触发因素。出乎意料的是,这些研究中的许多未获得最佳结果,表明需要优化与最佳临床方案相结合的许多不同的NK细胞参数。在选择最佳的免疫治疗药物之前,必须考虑各种参数,包括NK细胞具有的大量激活受体,选择用于治疗患者的NK细胞的来源,取决于靶细胞的NK细胞激活的不同细胞毒性机制和肿瘤细胞的生存机制。使用NK细胞的策略。在这篇综述中,我们将讨论这些参数,以帮助改善在癌症治疗中使用NK细胞的当前策略。此外,将在NK细胞的背景下讨论彻底改变免疫疗法概念的嵌合抗原受体(CAR)修饰。最后,还将讨论NK细胞的阴暗面及其与炎症的关系。

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