4.6 Review

NK cells shape pancreatic and oral tumor microenvironments; role in inhibition of tumor growth and metastasis

Journal

SEMINARS IN CANCER BIOLOGY
Volume 53, Issue -, Pages 178-188

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2018.08.001

Keywords

Natural killer (NK) cells; Cancer stem cells (CSCs); Differentiation; Cancer immunotherapy; Super-charged NK cells; Sonicated AJ2; Humanized-BLT (hu-BLT) mice; IFN-gamma; Cytotoxicity

Categories

Funding

  1. NIH [R01DE12880, RO1DE022552]
  2. UCLA Academic senate
  3. School of Dentistry, XO club, Pingan APD (Beijing) Biomedical Technology Co. (PAPD)

Ask authors/readers for more resources

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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available