| First Author | Jewett A | Year | 2018 |
| Journal | Semin Cancer Biol | Volume | 53 |
| Pages | 178-188 | PubMed ID | 30081230 |
| Mgi Jnum | J:267418 | Mgi Id | MGI:6259289 |
| Doi | 10.1016/j.semcancer.2018.08.001 | Citation | Jewett A, et al. (2018) NK cells shape pancreatic and oral tumor microenvironments; role in inhibition of tumor growth and metastasis. Semin Cancer Biol 53:178-188 |
| abstractText | We have recently shown that natural killer (NK) cells select and differentiate cancer stem cells (CSCs)/undifferentiated tumors via secreted and membrane bound IFN-gamma (IFN-gamma) and TNF-alpha (TNF-alpha), preventing tumor growth and inducing remodeling of the tumor microenvironment. Since many conventional therapeutic strategies, including chemotherapy and radiotherapy remain fairly unsuccessful in treating CSCs/poorly differentiated tumors, there has been an increasing interest in NK cell-targeted immunotherapy for the treatment of aggressive tumors. In our recent studies, we used humanized-BLT (hu-BLT) mouse model with transplanted human bone marrow, liver and thymus to demonstrate the efficacy of adoptive transfer of ex vivo expanded, super-charged NK cells in selection and differentiation of stem-like tumors within the context of a fully reconstituted human immune system. Furthermore, we have demonstrated that CSCs differentiated with split-anergized NK cells prior to implantation in hu-BLT mice were not able to grow or metastasize. However, when NK cell-mediated tumor differentiation was blocked by the addition of antibodies to IFN-gamma and TNF-alpha, tumors grew and metastasized. In this review, we present current advances in NK cell expansion and therapeutic delivery, and discuss the utility of allogeneic super-charged NK cells in treatment of cancer patients. In addition, NK suppression occurs not only at the stage of overt cancer, but also at the pre-neoplastic stage. Therefore, due to the indispensable role of NK cells in targeting CSCs/undifferentiated tumors and their role in differentiation of the tumors, NK cells should be placed high in the armamentarium of tumor immunotherapy. |
