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Natural Killer Cells: Diverse Functions in Tumor Immunity and Defects in Pre-neoplastic and Neoplastic Stages of Tumorigenesis.
Molecular Therapy: Oncology ( IF 5.7 ) Pub Date : 2019-11-29 , DOI: 10.1016/j.omto.2019.11.002
Anahid Jewett 1, 2 , Janko Kos 3, 4 , Kawaljit Kaur 1 , Tahmineh Safaei 1 , Christine Sutanto 1 , Wuyang Chen 1 , Paul Wong 1 , Artin Keshishian Namagerdi 1 , Changge Fang 5 , Yuman Fong 6, 7, 8 , Meng-Wei Ko 1
Affiliation  

Natural killer (NK) cells are the key immune effectors with the ability to mediate selection and differentiation of a number of different cancer stem cells/undifferentiated tumors via lysis, and secreted or membrane-bound interferon (IFN)-γ and tumor necrosis factor (TNF)-α, respectively, leading to curtailment of tumor growth and metastasis. In this review, we present an overview of our recent findings on the biology and significance of NK cells in selection and differentiation of stem-like tumors using in vitro and in vivo studies conducted in humanized-BLT mice and in cancer patients. In addition, we present current advances in NK cell expansion and therapeutic delivery, and discuss the utility of allogeneic supercharged NK cells in the treatment of cancer patients. Moreover, we discuss the potential loss of NK cell numbers and function at the neoplastic and pre-neoplastic stages of tumorigenesis in induction and progression of pancreatic cancer. Therefore, because of their indispensable role in targeting cancer stem-like/undifferentiated tumors, NK cells should be placed high in the armamentarium of tumor immunotherapy. A combination of allogeneic supercharged NK cells with other immunotherapeutic strategies such as oncolytic viruses, antibody-dependent cellular cytotoxicity (ADCC)-inducing antibodies, checkpoint inhibitors, chimeric antigen receptor (CAR) T cells, CAR NK cells, and chemotherapeutic and radiotherapeutic strategies can be used for the ultimate goal of tumor eradication.



中文翻译:

天然杀伤细胞:肿瘤免疫的多种功能以及肿瘤发生前肿瘤和肿瘤发展阶段的缺陷。

天然杀伤(NK)细胞是关键的免疫效应物,能够通过裂解,分泌或膜结合干扰素(IFN)-γ和肿瘤坏死因子介导许多不同的癌症干细胞/未分化肿瘤的选择和分化。 TNF)-α分别导致肿瘤生长和转移的减少。在这篇综述中,我们概述了我们最近关于NK细胞的生物学及其在体外体内选择和分化干样肿瘤中的意义的生物学意义的概述。在人源化BLT小鼠和癌症患者中进行的研究。此外,我们介绍了NK细胞扩增和治疗性递送方面的最新进展,并讨论了异体增压NK细胞在治疗癌症患者中的实用性。此外,我们讨论了在胰腺癌的诱导和发展过程中,在肿瘤发生的赘生性和赘生性阶段,NK细胞数量和功能的潜在丧失。因此,由于其在靶向癌干样/未分化肿瘤中不可或缺的作用,NK细胞应置于肿瘤免疫疗法的武器库中。将同种异体增压NK细胞与其他免疫治疗策略(例如溶瘤病毒,诱导抗体依赖性细胞毒性(ADCC)的抗体,检查点抑制剂,

更新日期:2019-11-29
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