Abstract
Mounting effective anti-tumor immune responses by cytotoxic effectors is important for the clearance of tumors. However, accumulated evidence suggests that the cytotoxic function of immune effectors is largely suppressed in the tumor microenvironment by a number of distinct effectors and their secreted factors. The aims of this review are to provide a rationale and potential mechanism for immunosuppression in cancer, and to demonstrate the significance of such immunosuppression in cellular differentiation and tissue regeneration in pathological conditions, and progression of cancer. We have recently shown that increased NK cell function was seen when they were cultured with primary oral squamous carcinoma stem cells (OSCSCs) as compared to their more differentiated oral squamous carcinoma cells (OSCCs). In addition, human embryonic stem cells (hESCs), Mesenchymal Stem Cells (hMSCs), dental pulp stem cells (hDPSCs) and induced pluripotent stem cells (hiPSCs) were significantly more susceptible to NK cell mediated cytotoxicity than their differentiated counterparts or parental cells from which they were derived. We have also reported that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NFκB or targeted knock down of COX2 augmented NK cell function significantly. Total population of monocytes and those depleted of CD16(+) subsets were able to substantially prevent NK cell mediated lysis of OSCSCs, MSCs and DPSCs. Taken together, our results suggest that stem cells are significant targets of the NK cell cytotoxicity. The concept of split anergy in NK cells and its contribution to tissue repair and regeneration and in tumor resistance and progression will be discussed in this review. Therefore, patients with cancer may benefit from repeated allogeneic NK cell transplantation at the site of the tumor for specific elimination of cancer stem cells.
Keywords: Apoptosis, NFκB, Differentiation, immunosuppression, NK, IL-6, split anergy, cancer stem cells, Natural Killer cells, Stem cells, TNF-, IFN, MDSCs, Monocytes
Current Drug Delivery
Title: Natural Killer Cells Preferentially Target Cancer Stem Cells; Role of Monocytes in Protection Against NK Cell Mediated Lysis of Cancer Stem Cells
Volume: 9 Issue: 1
Author(s): Anahid Jewett, Han-Ching Tseng, Aida Arasteh, Saba Saadat, Russell E. Christensen and Nicholas A. Cacalano
Affiliation:
Keywords: Apoptosis, NFκB, Differentiation, immunosuppression, NK, IL-6, split anergy, cancer stem cells, Natural Killer cells, Stem cells, TNF-, IFN, MDSCs, Monocytes
Abstract: Mounting effective anti-tumor immune responses by cytotoxic effectors is important for the clearance of tumors. However, accumulated evidence suggests that the cytotoxic function of immune effectors is largely suppressed in the tumor microenvironment by a number of distinct effectors and their secreted factors. The aims of this review are to provide a rationale and potential mechanism for immunosuppression in cancer, and to demonstrate the significance of such immunosuppression in cellular differentiation and tissue regeneration in pathological conditions, and progression of cancer. We have recently shown that increased NK cell function was seen when they were cultured with primary oral squamous carcinoma stem cells (OSCSCs) as compared to their more differentiated oral squamous carcinoma cells (OSCCs). In addition, human embryonic stem cells (hESCs), Mesenchymal Stem Cells (hMSCs), dental pulp stem cells (hDPSCs) and induced pluripotent stem cells (hiPSCs) were significantly more susceptible to NK cell mediated cytotoxicity than their differentiated counterparts or parental cells from which they were derived. We have also reported that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NFκB or targeted knock down of COX2 augmented NK cell function significantly. Total population of monocytes and those depleted of CD16(+) subsets were able to substantially prevent NK cell mediated lysis of OSCSCs, MSCs and DPSCs. Taken together, our results suggest that stem cells are significant targets of the NK cell cytotoxicity. The concept of split anergy in NK cells and its contribution to tissue repair and regeneration and in tumor resistance and progression will be discussed in this review. Therefore, patients with cancer may benefit from repeated allogeneic NK cell transplantation at the site of the tumor for specific elimination of cancer stem cells.
Export Options
About this article
Cite this article as:
Jewett Anahid, Tseng Han-Ching, Arasteh Aida, Saadat Saba, E. Christensen Russell and A. Cacalano Nicholas, Natural Killer Cells Preferentially Target Cancer Stem Cells; Role of Monocytes in Protection Against NK Cell Mediated Lysis of Cancer Stem Cells, Current Drug Delivery 2012; 9 (1) . https://dx.doi.org/10.2174/156720112798375989
DOI https://dx.doi.org/10.2174/156720112798375989 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advances of natural products, bio-actives and novel drug delivery system against emerging viral infections
Due to the increasing prevalence of viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compounds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable ...read more
Electrospun Fibers as Drug Delivery Systems
In recent years, electrospun fibers have attracted considerable attention as potential platforms for drug delivery due to their distinctive properties and adaptability. These fibers feature a notable surface area-to-volume ratio and can be intentionally designed with high porosity, facilitating an increased capacity for drug loading and rendering them suitable for ...read more
Emerging Nanotherapeutics for Mitigation of Neurodegenerative Disorders
Conditions affecting the central nervous system (CNS) present a significant hurdle due to limited access of both treatments and diagnostic tools for the brain. The blood-brain barrier (BBB) acts as a barrier, restricting the passage of molecules from the bloodstream into the brain. The most formidable challenge facing scientists is ...read more
Nanotechnology Based Chemotherapy for the treatment of Head & Neck Cancer
The escalating recurrence rates observed in Head and Neck cancer, particularly within the chemo-therapeutically treated cohort (50-60%), can be attributed to the non-selective nature of current anticancer drug delivery modalities. In this context, nanotechnology-based drug delivery systems emerge as a promising avenue for achieving precise localization of therapeutic agents to ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
New Molecules as Drug Candidates for the Treatment of Upper and Lower GI Tract Ulcers
Current Pharmaceutical Design Obesity in the Patient with Lung Disease
Current Respiratory Medicine Reviews Ocular Toxicities in Cancer Therapy: Still Overlooked
Current Cancer Therapy Reviews Targeting the Cancer Biomarker CD47: A Review on the Diverse Mechanisms of the CD47 Pathway in Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry The Use of Nimesulide and Its Analogues in Cancer Chemoprevention
Anti-Cancer Agents in Medicinal Chemistry Biological Role of Formaldehyde, and Cycles Related to Methylation, Demethylation, and Formaldehyde Production
Mini-Reviews in Medicinal Chemistry Metallothioneins and Cancer
Current Protein & Peptide Science Analysis of Oxaliplatin Resistance in Colorectal Cancer Cells by Combined Proteomics and Phosphoproteomic
Current Proteomics HER3 and its Ligand, Heregulin, as Targets for Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Nitric Oxide and Dietary Factors: Part III Minerals, Vitamins and Other Dietary and Lifestyle Factors
Vascular Disease Prevention (Discontinued) Eicosanoids in Prevention and Management of Diseases
Current Molecular Medicine Genetic and Epigenetic Studies for Determining Molecular Targets of Natural Product Anticancer Agents
Current Cancer Drug Targets Application of Genetic Polymorphisms in DNA Repair in the Prediction of Cancer Susceptibility and Clinical Outcome
Current Pharmacogenomics Small Molecule Inhibitors of NF-κB and JAK/STAT Signal Transduction Pathways as Promising Anti-Inflammatory Therapeutics
Mini-Reviews in Medicinal Chemistry Signaling Mechanism(S) of Reactive Oxygen Species in Epithelial-Mesenchymal Transition Reminiscent of Cancer Stem Cells in Tumor Progression
Current Stem Cell Research & Therapy Cytostatic and Apoptotic Effects of DNMT and HDAC Inhibitors in Endometrial Cancer Cells
Current Pharmaceutical Design Design, Synthesis and Biological Evaluation of Camptothecin Conjugated with NSAIDs as Novel Dual-actin Antitumor Agents
Letters in Drug Design & Discovery Signs and Related Mechanisms of Ethanol Hepatotoxicity
Current Drug Abuse Reviews Targeting RhoA/Rho Kinase and p21-Activated Kinase Signaling to Prevent Cancer Development and Progression
Recent Patents on Anti-Cancer Drug Discovery Towards Tyrosine Metabolism in Esophageal Squamous Cell Carcinoma
Combinatorial Chemistry & High Throughput Screening