Natural killer (NK) cells are known to select and differentiate cancer stem-like cells/undifferentiated tumors via lysis, and secreted/membrane bound IFN-gamma and TNF-alpha respectively, resulting in the control of tumor growth. Several in vivo mouse models including humanized-BLT mice have been used to study the biology and significance of NK cells in selection/differentiation of stem-like tumors within the context of a reconstituted human immune system. In addition, we discuss the evidence and significance of NK cell loss at the pre-neoplastic stage. Therefore, because of their indispensable role in targeting CSCs/undifferentiated tumors, NK-cells should be placed high in the armamentarium of tumor therapy.

Author Info: (1) Division of Oral Biology and Oral Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA, Los Angeles, CA, USA. (2) Department of Biotechnology, J ozef Stefan Institute, Ljubljana, Slovenia. (3) Division of Oral Biology and Oral Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA, Los Angeles, CA, USA. (4) Division of Oral Biology and Oral Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA, Los Angeles, CA, USA. (5) Department of Biotechnology, Jozef Stefan Institute, Ljubljana, Slovenia; Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia. (6) Division of Oral Biology and Oral Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA, Los Angeles, CA, USA; The Jonsson Comprehensive Cancer Center, UCLA School of Dentistry and Medicine, Los Angeles, CA, USA. Electronic address: ajewett@ucla.edu.