Stem Cell Niche, the Microenvironment and Immunological Crosstalk

Law, S.K. Alex; Chaudhuri, Surabhi

doi:10.1038/cmi.2008.13

Cited by 13 publications

(7 citation statements)

References 62 publications

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“…Recent studies showed that stem cells exhibit cytotoxic and phagocytic activities [20,21] and have a machinery for antigen presentation contrary to the previous concept that they are immunologically null [22]. This notion is further supported by presence of immune reactions to stem cells that are implanted for the sake of cell replacement in degenerative disease animal models.…”

Section: Immunogenicity Of Embryonic Stem Cellscontrasting

confidence: 48%

Do Cancer Stem Cells have an Immunomodulatory Role Different from the Bulk of Tumor Cells?

Ghebeh

Al‐Alwan²

2013

J Carcinogene Mutagene

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Cancer is one of the leading causes of death worldwide. In normal settings, the immune system is responsible for clearing cancer cells from our body. However, many patients develop immune tolerance to tumor cells through upregulation of immune regulatory molecules, release of immune suppressive factors in the tumor microenvironment and/or recruitment of regulatory/suppressive cells that impede the function of other fully activated effector immune cells. In spite of significant progress that have been achieved in increasing our understanding in this field, it is unknown whether all tumor cells exert similar inhibitory effect on the immune system or only specific subset(s) of tumor cells possess this feature.There is accumulating evidence that cancer is originated and sustained by a small population of cells called "Cancer Stem Cells (CSCs)". These cells share many characteristics of the normal stem cells including the selfrenewing ability. Thus, it is possible that they also have the immune privilege properties of normal stem cells. At least this has been shown to be the case for two types of cancers: melanoma and glioma.In this report we will review the role of CSCs in the creation of immune suppressive microenvironment which finally leads to tumor escape from the immune system surveillance.

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Section: Immunogenicity Of Embryonic Stem Cellscontrasting

confidence: 48%

Do Cancer Stem Cells have an Immunomodulatory Role Different from the Bulk of Tumor Cells?

Ghebeh

Al‐Alwan²

2013

J Carcinogene Mutagene

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“…The inhibitory status of the TME largely impairs the effect of immunotherapy. 29 The intensity of the immune response in the TME crucially determines the effectiveness of immunotherapy. 3–5,30 The microenvironment in tumors that are MSI-H/dMMR is immune responsive, which provides evidence and a reference for other strategies.…”

Section: Discussionmentioning

confidence: 99%

Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment

Wang

et al. 2018

Cell Mol Immunol

108

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PD-1 blockade has demonstrated impressive clinical outcomes in colorectal cancers that have high microsatellite instability. However, the therapeutic efficacy for patients with tumors with low microsatellite instability or stable microsatellites needs further improvement. Here, we have demonstrated that low-dose decitabine could increase the expression of immune-related genes such as major histocompatibility complex genes and cytokine-related genes as well as the number of lymphocytes at the tumor site in CT26 colorectal cancer-bearing mice. A more significant inhibition of tumor growth and a prolongation of survival were observed in the CT26 mouse model after treatment with a combination of PD-1 blockade and decitabine than in mice treated with decitabine or PD-1 blockade alone. The anti-tumor effect of the PD-1 blockade was enhanced by low-dose decitabine. The results of RNA sequencing and whole-genome bisulfite sequencing of decitabine-treated CT26 cells and tumor samples with microsatellite stability from the patient tumor-derived xenograft model have shown that many immune-related genes, including antigen-processing and antigen-presenting genes, were upregulated, whereas the promoter demethylation was downregulated after decitabine exposure. Therefore, decitabine-based tumor microenvironment re-modulation could improve the effect of the PD-1 blockade. The application of decitabine in PD-1 blockade-based immunotherapy may elicit more potent immune responses, which can provide clinical benefits to the colorectal cancer patients with low microsatellite instability or stable microsatellites.

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“…1). 2 These factors present themselves to stem cells in the forms of cell-cell interactions, cell-matrix interactions, autocrine and paracrine signaling, and interaction with their mechanical David Ellison David Ellison is a PhD candidate in the Department of Biomedical Engineering at Johns Hopkins University. His research investigates the autocrine and paracrine signaling of mouse embryonic stem cells using a combined computational model and microfluidic device.…”

Section: Introductionmentioning

confidence: 99%

Lab-on-a-chip devices as an emerging platform for stem cell biology

et al. 2010

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The advent of stem cell based therapies has brought regenerative medicine into an increased focus as a part of the modern medicine practice, with a potential to treat a myriad of intractable diseases in the future. Stem cells reside in a complex microenvironment presenting them with a multitude of potential cues that are chemical, physical, and mechanical in nature. Conventional techniques used for experiments involving stem cells can only poorly mimic the physiological context, and suffer from imprecise spatial and temporal control, low throughput, lack of scalability and reproducibility, and poor representation of the mechanical and physical cell microenvironment. Novel lab-on-a-chip platforms, on the other hand, can much better mimic the complexity of in vivo tissue milieu and provide a greater control of the parameter variation in a high throughput and scalable manner. This capability may be especially important for understanding the biology and cementing the clinical potential of stem cell based therapies. Here we review microfabrication- and microfluidics-based approaches to investigating the complex biology of stem cell responses to changes in the local microenvironment. In particular, we categorize each method based on the types of controlled inputs it can have on stem cells, including soluble biochemical factors, extracellular matrix interactions, homotypic and heterotypic cell-cell signaling, physical cues (e.g. oxygen tension, pH, temperature), and mechanical forces (e.g. shear, topography, rigidity). Finally, we outline the methods to perform large scale observations of stem cell phenotypes and high-throughput screening of cellular responses to a combination of stimuli, and many new emerging technologies that are becoming available specifically for stem cell applications.

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Stem Cell Niche, the Microenvironment and Immunological Crosstalk

Cited by 13 publications

References 62 publications

Do Cancer Stem Cells have an Immunomodulatory Role Different from the Bulk of Tumor Cells?

Do Cancer Stem Cells have an Immunomodulatory Role Different from the Bulk of Tumor Cells?

Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment

Lab-on-a-chip devices as an emerging platform for stem cell biology

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