Mesenchymal stromal cells shape the MDS microenvironment by inducing suppressive monocytes that dampen NK cell function

Sarhan, Dhifaf; Wang, Jinhua; Arvindam, Upasana Sunil; Hallstrom, Caroline; Verneris, Michael R.; Grzywacz, Bartosz; Warlick, Erica D.; Blazar, Bruce R.; Miller, Jeffrey S.

doi:10.1172/jci.insight.130155

Cited by 38 publications

(31 citation statements)

References 48 publications

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“…These MDSCs produce high levels of cytosolic ROS, due to the action of NADPH oxidase (NOX2). This environment appears to maintain MDSCs in an undifferentiated state with immunosuppressive properties (78). In allogeneic HSCT, NOX2-mediated ROS production in MDSCs has been poorly described (25).…”

Section: Discussion and Future Considerationsmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells in the Context of Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2020

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Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses. In the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), MDSCs (in the donor graft and in the recipient, after allo-HSCT) might mediate immune suppression through multiple mechanisms. However, it remains unclear how MDSCs can be distinguished from their normal myeloid counterparts in the hematopoietic stem cell donor graft and during immune reconstitution after allo-HSCT in the recipient. Our ability to understand their exact role in allo-HSCT is limited by the absence of a specific gene signature or surface markers for identifying MDSCs among myeloid cells and by their plasticity in different microenvironments. According to various studies, MDSCs might induce transplant tolerance and control graft vs. host disease (GVHD), but their impact on the graft vs. tumor effect (GVT) is not fully understood. In fact, we know that MDSCs commonly expand in patients with cancer, and they are thought to promote hematological malignancy progression. However, little is known about whether depleting them might be an effective strategy for enhancing GVT effects. Here, we review data published over the past 40 years on allo-HSCT to delineate the different MDSC subsets, and their abilities to induce transplant tolerance and preserve the GVT effect. This review will provide a basis for determining whether one MDSC subset might be proposed as the most appropriate candidate for cellular therapies, due to its ability to modulate GVHD.

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Section: Discussion and Future Considerationsmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells in the Context of Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2020

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“…In MDSs and AML secondary to Fanconi anemia, MSCs exert an immunosuppressive action via increased production of prostaglandins, which are able to reduce T-cell immunity against leukemic cells [ 101 ]. More recently, MDS–MSCs were shown to inhibit NK cells, which are pivotal for cancer immune surveillance [ 102 ]. Finally, neoplastic MSCs are able to switch from MSC Type-1 (proinflammatory) to “tumor-educated” MSC Type-2 cells (anti-inflammatory) that exhibit stronger immunosuppressive and migratory properties and promote proliferation and drug resistance [ 103 ].…”

Section: The Role Of Mesenchymal Stem Cells In Myelodysplastic Synmentioning

confidence: 99%

Mesenchymal Stem Cells in Aplastic Anemia and Myelodysplastic Syndromes: The “Seed and Soil” Crosstalk

Fattizzo

Giannotta

Barcellini

2020

IJMS

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There is growing interest in the contribution of the marrow niche to the pathogenesis of bone marrow failure syndromes, i.e., aplastic anemia (AA) and myelodysplastic syndromes (MDSs). In particular, mesenchymal stem cells (MSCs) are multipotent cells that contribute to the organization and function of the hematopoietic niche through their repopulating and supporting abilities, as well as immunomodulatory properties. The latter are of great interest in MDSs and, particularly, AA, where an immune attack against hematopoietic stem cells is the key pathogenic player. We, therefore, conducted Medline research, including all available evidence from the last 10 years concerning the role of MSCs in these two diseases. The data presented show that MSCs display morphologic, functional, and genetic alterations in AA and MDSs and contribute to immune imbalance, ineffective hematopoiesis, and leukemic evolution. Importantly, adoptive MSC infusion from healthy donors can be exploited to heal the “sick” niche, with even better outcomes if cotransplanted with allogeneic hematopoietic stem cells. Finally, future studies on MSCs and the whole microenvironment will further elucidate AA and MDS pathogenesis and possibly improve treatment.

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“…In the affected BM microenvironment CXCL8 is mainly secreted by MSCs ( Cheng et al, 2019 ). Study on other bone marrow disorders show that and MSCs to shape the Microenvironment at least partly by inducing suppressive monocytes and dampening NK cell functions ( Sarhan et al, 2020 ).…”

Section: Msc Pro-tumorigenic Effects: Immunosuppression and Metabolicmentioning

confidence: 99%

Tumor Microenvironment Uses a Reversible Reprogramming of Mesenchymal Stromal Cells to Mediate Pro-tumorigenic Effects

Kamdje

Etet

Tagne

et al. 2020

Front. Cell Dev. Biol.

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The role of mesenchymal stromal cells (MSCs) in the tumor microenvironment is well described. Available data support that MSCs display anticancer activities, and that their reprogramming by cancer cells in the tumor microenvironment induces their switch toward pro-tumorigenic activities. Here we discuss the recent evidence of pro-tumorigenic effects of stromal cells, in particular (i) MSC support to cancer cells through the metabolic reprogramming necessary to maintain their malignant behavior and stemness, and (ii) MSC role in cancer cell immunosenescence and in the establishment and maintenance of immunosuppression in the tumor microenvironment. We also discuss the mechanisms of tumor microenvironment mediated reprogramming of MSCs, including the effects of hypoxia, tumor stiffness, cancer-promoting cells, and tumor extracellular matrix. Finally, we summarize the emerging strategies for reprogramming tumor MSCs to reactivate anticancer functions of these stromal cells.

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Mesenchymal stromal cells shape the MDS microenvironment by inducing suppressive monocytes that dampen NK cell function

Cited by 38 publications

References 48 publications

Myeloid-Derived Suppressor Cells in the Context of Allogeneic Hematopoietic Stem Cell Transplantation

Myeloid-Derived Suppressor Cells in the Context of Allogeneic Hematopoietic Stem Cell Transplantation

Mesenchymal Stem Cells in Aplastic Anemia and Myelodysplastic Syndromes: The “Seed and Soil” Crosstalk

Tumor Microenvironment Uses a Reversible Reprogramming of Mesenchymal Stromal Cells to Mediate Pro-tumorigenic Effects

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