We have previously demonstrated that natural killer (NK) cells are the main immune effectors that can mediate selection and differentiation of different cancer stem cells and undifferentiated tumors via lysis and secreted or membrane-bound interferon-γ and tumor necrosis factor-α, respectively. This leads to growth inhibition and tumor metastasis curtailment. In this review, we present an overview of our findings on NK cell biology and its significance in selection and differentiation of stem-like tumors using in vitro and in vivo studies conducted in nonobese diabetic/severe combined immunodeficiency (scid)/interleukin-Rγ^--, humanized−bone-marrow/liver/thymus (hu-BLT) mice, and those of human cancer patients. Moreover, we present recent advances in NK cell expansion and therapeutic delivery and discuss the superiority of allogeneic supercharged NK cells over their autologous counterparts for cancer treatment. We review potential loss of NK cell numbers and function at neoplastic and preneoplastic stages of tumorigenesis as a potential mechanism for pancreatic cancer induction and progression. We believe that NK cells should be placed highly in the armamentarium of tumor immunotherapy due to their indispensable role in targeting cancer stem-like/poorly differentiated tumors and a variety of other key NK cell functions that are discussed in this report, including their role in CD8⁺ T-cell expansion and targeting gene knockout or dedifferentiated tumors. The combination of allogeneic supercharged NK cells and other immunotherapeutic strategies such as oncolytic viruses, antibody-dependent cellular cytotoxicity-inducing antibodies, checkpoint inhibitors, chimeric antigen receptor (CAR)-T cells and CAR-NK cells, chemotherapeutics, and radiotherapeutic strategies can be used for optimal eradication of tumors.

中文翻译：

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癌症患者中天然杀伤细胞的多种缺陷：无政府状态，全身免疫失调和转移性癌症的免疫抑制。

先前我们已经证明，自然杀伤（NK）细胞是主要的免疫效应因子，可以分别通过裂解，分泌或膜结合干扰素-γ和肿瘤坏死因子-α介导不同癌症干细胞和未分化肿瘤的选择和分化。这导致生长抑制和肿瘤转移减少。在这篇综述中，我们概述了我们在非肥胖型糖尿病/重度联合免疫缺陷症（scid）/白细胞介素-Rγ中进行的体外和体内研究中有关NK细胞生物学及其在干细胞样肿瘤选择和分化中的意义的研究结果^{- --}，人源化的骨髓/肝/胸腺（hu-BLT）小鼠以及人类癌症患者的小鼠。此外，我们目前在NK细胞扩增和治疗交付方面的最新进展，并讨论了同种异体增压NK细胞在其自体对应物上用于癌症治疗的优越性。我们审查了潜在的NK细胞数量和肿瘤形成的肿瘤和肿瘤前阶段的功能丧失，作为胰腺癌诱导和进展的潜在机制。我们认为，由于NK细胞在靶向癌干样/分化差的肿瘤中起着不可或缺的作用，并且在本报告中讨论了多种其他关键NK细胞功能，包括它们在肿瘤免疫治疗中的作用，因此应将它们高度放在肿瘤免疫疗法的武器库中。 CD8 ⁺T细胞扩增和靶向基因敲除或去分化的肿瘤。可以将同种异体增压NK细胞与其他免疫治疗策略（例如溶瘤病毒，抗体依赖性细胞毒性诱导抗体，检查点抑制剂，嵌合抗原受体（CAR）-T细胞和CAR-NK细胞），化学疗法和放射治疗策略结合起来使用用于最佳根除肿瘤。