The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, University of California, Los Angeles, CA, 90095-1668, USA.
Division of Oral Biology and Medicine, UCLA School of Dentistry, University of California, 10833 Le Conte Ave, Los Angeles, CA, 90095-1668, USA.
Cancer Immunol Immunother. 2012 Feb;61(2):265-274. doi: 10.1007/s00262-011-1163-7. Epub 2011 Nov 25.
Cytotoxic function of NK cells is largely suppressed in the tumor microenvironment by a number of distinct effectors and their secreted factors. The aims of this review are to provide a rationale and a potential mechanism for immunosuppression in cancer and to demonstrate the significance of such immunosuppression in cellular differentiation and progression of cancer. We have recently shown that NK cells mediate significant cytotoxicity against primary oral squamous carcinoma stem cells (OSCSCs) as compared to their more differentiated oral squamous carcinoma cells. In addition, human embryonic stem cells, mesenchymal stem cells (hMSCs), dental pulp stem cells (hDPSCs) and induced pluripotent stem cells were all significantly more susceptible to NK-cell-mediated cytotoxicity than their differentiated counterparts or parental cells from which they were derived. We have also reported that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NFκB significantly augmented NK-cell function. Total population of monocytes and those depleted of CD16+ subsets were able to substantially suppress NK-cell-mediated lysis of OSCSCs, hMSCs and hDPSCs. Overall, our results suggest that stem cells but not their differentiated counterparts are significant targets of the NK-cell cytotoxicity. The concept of split anergy in NK cells and its contribution to cell differentiation, tissue repair and regeneration and in tumor resistance and progression will be discussed in this review.
NK 细胞的细胞毒性功能在肿瘤微环境中被许多不同的效应器及其分泌因子所抑制。本综述的目的是为癌症中的免疫抑制提供一个基本原理和潜在机制，并证明这种免疫抑制在细胞分化和癌症进展中的重要性。我们最近表明，与分化程度更高的口腔鳞状细胞癌细胞相比，NK 细胞对原发性口腔鳞状癌干细胞（OSCSC）具有显著的细胞毒性。此外，人类胚胎干细胞、间充质干细胞（hMSCs）、牙髓干细胞（hDPSCs）和诱导多能干细胞对 NK 细胞介导的细胞毒性的敏感性都明显高于其分化细胞或起源细胞。我们还报告称，通过阻断 NFκB 抑制细胞分化或逆转为分化程度较低的表型可显著增强 NK 细胞的功能。单核细胞的总群体和耗尽 CD16+亚群的单核细胞能够显著抑制 NK 细胞介导的 OSCSC、hMSC 和 hDPSC 的裂解。总体而言，我们的结果表明，干细胞而不是其分化细胞是 NK 细胞细胞毒性的重要靶点。本文将讨论 NK 细胞中的分裂性无能及其对细胞分化、组织修复和再生以及肿瘤抵抗和进展的贡献。
