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NK cells shape pancreatic and oral tumor microenvironments; role in inhibition of tumor growth and metastasisJewett, Anahid ...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 was 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.Source: Seminars in cancer biology. - ISSN 1044-579X (Vol. 53, Dec. 2018, str. 178-188)Type of material - article, component partPublish date - 2018Language - englishCOBISS.SI-ID - 4563313
Author
Jewett, Anahid |
Kos, Janko, 1959- |
Fong, Yuman |
Ko, Meng-Wei |
Safaei, Tahmineh |
Perišić, Milica |
Kaur, Kawaljit
Topics
Imunoterapija |
Rak (medicina) |
Tumorji |
Citotoksičnost |
natural killer (NK) cell |
cancer stem cells (CSCs) |
differentiation |
cancer immunotherapy |
super-charged NK cell |
sonicated AJ2 |
humanized-BLT (hu-BLT) mice |
IFN-gamma |
cytotoxicity
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Jewett, Anahid | ![]() |
Kos, Janko, 1959- | 04648 |
Fong, Yuman | ![]() |
Ko, Meng-Wei | ![]() |
Safaei, Tahmineh | ![]() |
Perišić, Milica | 36596 |
Kaur, Kawaljit | ![]() |
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