Natural Killer Cells: Diverse Functions in Tumor Immunity and Defects in Pre-neoplastic and Neoplastic Stages of Tumorigenesis

Anahid Jewett; Janko Kos; Kawaljit Kaur; Tahmineh Safaei; Christine Sutanto; Wuyang Chen; Paul Wong; Artin Keshishian Namagerdi; Changge Fang; Yuman Fong; Meng-Wei Ko

doi:10.1016/j.omto.2019.11.002

Natural Killer Cells: Diverse Functions in Tumor Immunity and Defects in Pre-neoplastic and Neoplastic Stages of Tumorigenesis

Mol Ther Oncolytics. 2019 Nov 29:16:41-52. doi: 10.1016/j.omto.2019.11.002. eCollection 2020 Mar 27.

Authors

Anahid Jewett^{1

2}, Janko Kos^{3

4}, Kawaljit Kaur¹, Tahmineh Safaei¹, Christine Sutanto¹, Wuyang Chen¹, Paul Wong¹, Artin Keshishian Namagerdi¹, Changge Fang⁵, Yuman Fong^{6

7

8}, Meng-Wei Ko¹

Affiliations

¹ Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA, Los Angeles, CA, USA.
² The Jonsson Comprehensive Cancer Center, UCLA School of Dentistry and Medicine, Los Angeles, CA, USA.
³ Department of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia.
⁴ Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
⁵ APD-PAPD Center for NK Cell Therapy, Beijing, China.
⁶ Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA.
⁷ Center for Gene Therapy, Duarte, CA, USA.
⁸ Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.

Abstract

Natural killer (NK) cells are the key immune effectors with the ability to mediate selection and differentiation of a number of different cancer stem cells/undifferentiated tumors via lysis, and secreted or membrane-bound interferon (IFN)-γ and tumor necrosis factor (TNF)-α, respectively, leading to curtailment of tumor growth and metastasis. In this review, we present an overview of our recent findings on the biology and significance of NK cells in selection and differentiation of stem-like tumors using in vitro and in vivo studies conducted in humanized-BLT mice and in cancer patients. In addition, we present current advances in NK cell expansion and therapeutic delivery, and discuss the utility of allogeneic supercharged NK cells in the treatment of cancer patients. Moreover, we discuss the potential loss of NK cell numbers and function at the neoplastic and pre-neoplastic stages of tumorigenesis in induction and progression of pancreatic cancer. Therefore, because of their indispensable role in targeting cancer stem-like/undifferentiated tumors, NK cells should be placed high in the armamentarium of tumor immunotherapy. A combination of allogeneic supercharged NK cells with other immunotherapeutic strategies such as oncolytic viruses, antibody-dependent cellular cytotoxicity (ADCC)-inducing antibodies, checkpoint inhibitors, chimeric antigen receptor (CAR) T cells, CAR NK cells, and chemotherapeutic and radiotherapeutic strategies can be used for the ultimate goal of tumor eradication.

Keywords: CSCs; KRAS; NK cells; cancer immunotherapy; cancer stem cells; differentiation; humanized-BLT mice; osteoclasts; pre-neoplastic; supercharged NK cells.

Publication types

Review

Abstract

Publication types

Grants and funding