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Updated: Dec 31, 2025
Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
Natural Killer Cells: Diverse Functions in Tumor Immunity and Defects in Pre-neoplastic and Neoplastic Stages of
Anahid Jewett1,2, Janko Kos3,4, Kawaljit Kaur1
1Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA, Los Angeles, 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.
Insights
Natural killer (NK) cells are crucial for targeting cancer stem cells and inhibiting tumor growth. Enhancing NK cell therapies, including allogeneic supercharged NK cells, offers promising cancer treatment strategies.
Area of Science:
- Immunology
- Cancer Biology
- Cell Therapy
Background:
- Natural killer (NK) cells are vital immune effectors that target cancer stem cells.
- NK cells eliminate tumors via lysis and cytokine secretion (interferon-γ and tumor necrosis factor-α), inhibiting growth and metastasis.
Purpose of the Study:
- To review the role of NK cells in selecting and differentiating stem-like tumors.
- To discuss advances in NK cell expansion, therapeutic delivery, and allogeneic supercharged NK cell utility.
- To explore NK cell dysfunction in pancreatic cancer development.
Main Methods:
- Review of in vitro and in vivo studies.
- Analysis of data from humanized-BLT mice and cancer patients.
- Examination of NK cell biology and therapeutic applications.
Main Results:
- NK cells effectively target and differentiate cancer stem cells.
- Allogeneic supercharged NK cells show therapeutic potential.
- NK cell loss is implicated in pancreatic cancer progression.
Conclusions:
- NK cells are indispensable in targeting cancer stem-like tumors and should be prioritized in cancer immunotherapy.
- Combining supercharged NK cells with other therapies (e.g., oncolytic viruses, CAR T cells, checkpoint inhibitors) can enhance tumor eradication.
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