Mesenchymal stem cells derived from low risk acute lymphoblastic leukemia patients promote NK cell antitumor activity

Entrena, Ana; Varas, Alberto; Vázquez, Manuel; Melén, Gustavo J.; Fernández-Sevilla, Lidia M.; García‐Castro, Javier; Ramı́rez, Manuel; Zapata, A.; Vicente, Ángeles

doi:10.1016/j.canlet.2015.04.012

Cited by 16 publications

(15 citation statements)

References 34 publications

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“…Interestingly, contrasting with the idea that the stromal microenvironment protects tumor cells from NK cell attack, it has recently been shown that BMSC isolated from low-risk ALL patients promotes NK cell anti-tumor ability compared to healthy donors [119]. Indeed, ALL-derived stromal cells not only did not decrease activating receptors expression on NK cells, but also upregulated cytokine secretion, granule exocytosis, and cytotoxic functions.…”

Section: Msc and Tumor Cells: The Cross-talk Which Impairs Innate mentioning

confidence: 96%

“…Indeed, ALL-derived stromal cells not only did not decrease activating receptors expression on NK cells, but also upregulated cytokine secretion, granule exocytosis, and cytotoxic functions. Interestingly, this could occur since ALL-isolated stromal cells express co-stimulatory molecules such as CD40 and CD86, normally not expressed in healthy donors [55,119]. Moreover, stromal cells isolated from ALL patients display low/negative expression of PD-L1, which is expressed on other hematological malignancies-derived stromal cells.…”

Section: Msc and Tumor Cells: The Cross-talk Which Impairs Innate mentioning

confidence: 99%

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Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Poggi

Giuliani

2016

Vaccines

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The tumor microenvironment is a good target for therapy in solid tumors and hematological malignancies. Indeed, solid tumor cells’ growth and expansion can influence neighboring cells’ behavior, leading to a modulation of mesenchymal stromal cell (MSC) activities and remodeling of extracellular matrix components. This leads to an altered microenvironment, where reparative mechanisms, in the presence of sub-acute inflammation, are not able to reconstitute healthy tissue. Carcinoma cells can undergo epithelial mesenchymal transition (EMT), a key step to generate metastasis; these mesenchymal-like cells display the functional behavior of MSC. Furthermore, MSC can support the survival and growth of leukemic cells within bone marrow participating in the leukemic cell niche. Notably, MSC can inhibit the anti-tumor immune response through either carcinoma-associated fibroblasts or bone marrow stromal cells. Experimental data have indicated their relevance in regulating cytolytic effector lymphocytes of the innate and adaptive arms of the immune system. Herein, we will discuss some of the evidence in hematological malignancies and solid tumors. In particular, we will focus our attention on the means by which it is conceivable to inhibit MSC-mediated immune suppression and trigger anti-tumor innate immunity.

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Section: Msc and Tumor Cells: The Cross-talk Which Impairs Innate mentioning

confidence: 96%

Section: Msc and Tumor Cells: The Cross-talk Which Impairs Innate mentioning

confidence: 99%

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Poggi

Giuliani

2016

Vaccines

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“…In addition, the engagement of tool-like receptor (TLR) reverted M MSC toward a M1 phenotype with pro-inflammatory and immunostimulatory activities [ 58 ] thus becoming detrimental for tumor progression. Conversely, it has been reported that MSCs derived from bone marrow of patients with low/intermediate risk leukemia at diagnosis enhanced the NK cell antitumor cytolytic activity and their pro-inflammatory cytokine production [ 59 ].…”

Section: Mesenchymal Stem Cells Modulate Tumor Immune Responsementioning

confidence: 99%

Tumor-educated mesenchymal stem cells promote pro-metastatic phenotype

et al. 2017

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Multipotent mesenchymal stem cells (MSCs) are recruited into tumor microenvironment in response to multiple signals produced by cancer cells. Molecules involved in their homing to tumors are the same inflammatory mediators produced by injured tissues: chemokines, cytokines and growth factors. When MSCs arrive into the tumor microenvironment these are “educated” to have pro-metastatic behaviour. Firstly, they promote cancer immunosuppression modulating both innate and adaptive immune systems. Moreover, tumor associated-MSCs trans-differentiating into cancer-associated fibroblasts can induce epithelial-mesenchymal-transition program in tumor cells. This process determinates a more aggressive phenotype of cancer cells by increasing their motility and invasiveness and favoring their dissemination to distant sites. In addition, MSCs are involved in the formation and modelling of pre-metastatic niches creating a supportive environment for colonization of circulating tumor cells.The development of novel therapeutic approaches targeting the different functions of MSCs in promoting tumor progression as well as the mechanisms underlying their activities could enhance the efficacy of conventional and immune anti-cancer therapies.Furthermore, many studies report the use of MSCs engineered to express different genes or as vehicle to specifically deliver novel drugs to tumors exploiting their strong tropism. Importantly, this approach can enhance local therapeutic efficacy and reduce the risk of systemic side effects.

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“…Interestingly, MSCs isolated from cancer patients do not always attenuate the function of NK cells. In fact, MSCs isolated from acute lymphoblastic leukemia patients increased the cytotoxic functionality of NK cells to a greater extent than healthy MSCs [ 67 ]. The influence of MSCs on the recruitment of NK cells has also been considered a potential therapeutic strategy.…”

Section: The Interaction Of Mscs and The Immune System In The Tumomentioning

confidence: 99%

The Immunomodulatory Effects of Mesenchymal Stem Cell Polarization within the Tumor Microenvironment Niche

Rivera-Cruz

Shearer

Neto

et al. 2017

Stem Cells International

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Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly for their antitumor effects. This cell population can be isolated from multiple tissue sources and also display an innate ability to home to areas of inflammation, such as tumors. Upon entry into the tumor microenvironment niche, MSCs promote or inhibit tumor progression by various mechanisms, largely through the release of soluble factors. These factors can be immunomodulatory by activating or inhibiting both the adaptive and innate immune responses. The mechanisms by which MSCs modulate the immune response are not well understood. Because of this, the relationship between MSCs and immune cells within the tumor microenvironment niche continues to be an active area of research in order to help explain the apparent contradictory findings currently available in the literature. The ongoing research aims to enhance the potential of MSCs in future therapeutic applications.

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Mesenchymal stem cells derived from low risk acute lymphoblastic leukemia patients promote NK cell antitumor activity

Cited by 16 publications

References 34 publications

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Tumor-educated mesenchymal stem cells promote pro-metastatic phenotype

The Immunomodulatory Effects of Mesenchymal Stem Cell Polarization within the Tumor Microenvironment Niche

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