The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Oral Biology and Medicine, School of Dentistry, University of California Los Angeles, Los Angeles, CA 90095, USA.
The Jonsson Comprehensive Cancer Center, UCLA School of Dentistry and Medicine, Los Angeles, CA 90095, USA.
Cells. 2022 Feb 16;11(4):697. doi: 10.3390/cells11040697.
In this paper, we present the role of autologous and allogeneic monocytes from healthy individuals and those of the cancer patients, with a number of distinct cancers, in activating the function of natural killer (NK) cells, in particular, in induction of IFN-γ secretion by the NK cells and the functional capability of secreted IFN-γ in driving differentiation of the tumor cells. In addition, we compared the roles of CD16 signaling as well as sonicated probiotic bacteria AJ2 (sAJ2)-mediated induction and function of IFN-γ-mediated differentiation in tumor cells. We found that monocytes from cancer patients had lower capability to induce functional IFN-γ secretion by the autologous CD16 mAb-treated NK cells in comparison to those from healthy individuals. In addition, when patient monocytes were cultured with NK cells from healthy individuals, they had lower capability to induce functional IFN-γ secretion by the NK cells when compared to those from autologous monocyte/NK cultures from healthy individuals. Activation by sAJ2 or addition of monocytes from healthy individuals to patient NK cells increased the secretion of functional IFN-γ by the NK cells and elevated its functional capability to differentiate tumors. Monocytes from cancer patients were found to express lower CD16 receptors, providing a potential mechanism for their lack of ability to trigger secretion of functional IFN-γ. In addition to in vitro studies, we also conducted in vivo studies in which cancer patients were given oral supplementation of AJ2 and the function of NK cells were studied. Oral ingestion of AJ2 improved the secretion of IFN-γ by patient derived NK cells and resulted in the better functioning of NK cells in cancer patients. Thus, our studies indicate that for successful NK cell immunotherapy, not only the defect in NK cells but also those in monocytes should be corrected. In this regard, AJ2 probiotic bacteria may serve to provide a potential adjunct treatment strategy.
在本文中，我们介绍了来自健康个体和患有多种不同癌症的癌症患者的自体和同种异体单核细胞在激活自然杀伤 (NK) 细胞功能方面的作用，特别是在诱导 NK 细胞分泌 IFN-γ和分泌 IFN-γ的功能能力在驱动肿瘤细胞分化方面的作用。此外，我们比较了 CD16 信号以及超声处理的益生菌 AJ2 (sAJ2)介导的诱导和 IFN-γ介导的肿瘤细胞分化的功能作用。我们发现，与健康个体相比，癌症患者的单核细胞诱导自体 CD16 mAb 处理的 NK 细胞分泌功能性 IFN-γ的能力较低。此外，当患者单核细胞与来自健康个体的 NK 细胞共培养时，与来自健康个体的自体单核细胞/NK 共培养相比，它们诱导 NK 细胞分泌功能性 IFN-γ的能力较低。sAJ2 的激活或将健康个体的单核细胞添加到患者的 NK 细胞中，增加了 NK 细胞分泌功能性 IFN-γ的能力，并提高了其分化肿瘤的功能能力。发现癌症患者的单核细胞表达较低水平的 CD16 受体，这为其缺乏触发功能性 IFN-γ分泌的能力提供了潜在的机制。除了体外研究，我们还进行了体内研究，其中给癌症患者口服补充 AJ2 并研究了 NK 细胞的功能。口服 AJ2 改善了患者来源的 NK 细胞分泌 IFN-γ的能力，并使 NK 细胞在癌症患者中的功能更好。因此，我们的研究表明，为了成功进行 NK 细胞免疫治疗，不仅要纠正 NK 细胞的缺陷，还要纠正单核细胞的缺陷。在这方面，AJ2 益生菌可能是一种潜在的辅助治疗策略。
