Tolerogenic Role of Myeloid Suppressor Cells in Organ Transplantation

Ochando, Jordi; Conde, Patricia; Utrero‐Rico, Alberto; Paz‐Artal, Estela

doi:10.3389/fimmu.2019.00374

Cited by 25 publications

(20 citation statements)

References 85 publications

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“…The MDSCs are a heterogeneous group of myeloid cells able to suppress adaptive and innate immune responses and have been suggested as potential biomarkers for allograft tolerance. They were initially described in cancer, and several studies have pointed out MDSC to play an important role in the regulation of immune responses in other clinical setting, such as organ transplantation, infection, and autoimmune diseases (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy

et al. 2020

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Myeloid-derived suppressor cells (MDSC) represent a heterogeneous group of myeloid regulatory cells that were originally described in cancer. Several studies in animal models point to MDSC as important players in the induction of allograft tolerance due to their immune modulatory function. Most of the published studies have been performed in animal models, and the data addressing MDSCs in human organ transplantation are scarce. We evaluated the phenotype and function of different MDSCs subsets in 38 kidney transplant recipients (KTRs) at different time points. Our data indicate that monocytic MDSCs (Mo-MDSC) increase in KTR at 6 and 12 months posttransplantation. On the contrary, the percentages of polymorphonuclear MDSC (PMN-MDSC) and early-stage MDSC (e-MDSC) are not significantly increased. We evaluated the immunosuppressive activity of Mo-MDSC in KTR and confirmed their ability to increase regulatory T cells (Treg) in vitro. Interestingly, when we compared the ability of Mo-MDSC to suppress T cell proliferation, we observed that tacrolimus, but not rapamycin-treated KTR, was able to inhibit CD4 + T cell proliferation in vitro. This indicates that, although mTOR inhibitors are widely regarded as supportive of regulatory responses, rapamycin may impair Mo-MDSC function, and suggests that the choice of immunosuppressive therapy may determine the tolerogenic pathway and participating immune cells that promote organ transplant acceptance in KTR.

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Section: Introductionmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy

et al. 2020

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“…Myeloid-derived suppressor cells (MDSCs) are a heterogeneous myeloid cell population characterized by immune regulatory properties (21,22). The differentiation and accumulation of MDSCs in human beings depends on pathological conditions such as cancer (23), infection (24), autoimmunity (25) and transplantation (26) but occurs during physiological processes such as aging (27) and pregnancy (28). MDSCs can be divided at least in three main subgroups according to the expression of selective surface markers: monocytic MDSC (M-MDSCs), that are characterized as CD11b + Ly6C + Ly6G − cells in mouse and CD11b + CD14 + CD15 − HLA-DR low/− CD124 + cells in human; polymorphonuclear-MDSC (PMN-MDSCs), that are identified as CD11b + Ly6C − Ly6G + cells in tumor-bearing mice and CD11b + CD14 − CD15 + HLA-DR low/− CD124 + cells in cancer patients (when the analysis is performed in low density mononuclear cell fraction); finally, the last MDSC subset is composed by "early immature" MDSCs (eMDSCs) defined as CD11b + Gr1 + CCR2 + Sca1 + CD31 + cells in mouse and Lin − CD11b + CD34 + CD33 + CD117 + HLA-DR low/− cells in human (8,21,29).…”

Section: Mdsc: a Tumor-induced Myeloid Cell Subsetmentioning

confidence: 99%

The Engagement Between MDSCs and Metastases: Partners in Crime

et al. 2020

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Tumor metastases represent the major cause of cancer-related mortality, confirming the urgent need to identify key molecular pathways and cell-associated networks during the early phases of the metastatic process to develop new strategies to either prevent or control distal cancer spread. Several data revealed the ability of cancer cells to establish a favorable microenvironment, before their arrival in distant organs, by manipulating the cell composition and function of the new host tissue where cancer cells can survive and outgrow. This predetermined environment is termed "pre-metastatic niche" (pMN). pMN development requires that tumor-derived soluble factors, like cytokines, growth-factors and extracellular vesicles, genetically and epigenetically reprogram not only resident cells (i.e., fibroblasts) but also non-resident cells such as bone marrow-derived cells. Indeed, by promoting an "emergency" myelopoiesis, cancer cells switch the steady state production of blood cells toward the generation of pro-tumor circulating myeloid cells defined as myeloid-derived suppressor cells (MDSCs) able to sustain tumor growth and dissemination. MDSCs are a heterogeneous subset of myeloid cells with immunosuppressive properties that sustain metastatic process. In this review, we discuss current understandings of how MDSCs shape and promote metastatic dissemination acting in each fundamental steps of cancer progression from primary tumor to metastatic disease.

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“…The immunosuppressive function of MDSCs is a double-edged sword, and very different roles are noted under different circumstances [18] (Figure 2). For example, in organ transplantation, high levels of MDSCs inhibit CD8 + T cell-mediated graft-versus-host disease (GVHD) and translate to better graft survival [19][20][21]. However, in cancer, MDSCs are major contributors to tumorigenesis, metastasis, and development [22] (Figure 2).…”

Section: Immunosuppressive Activity Of Mdscs In the Tmementioning

confidence: 99%

Targeting Myeloid-Derived Suppressor Cells in Cancer Immunotherapy

Wang

Jia

et al. 2020

Cancers

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Myeloid-derived suppressor cells (MDSCs), which are activated under pathological conditions, are a group of heterogeneous immature myeloid cells. MDSCs have potent capacities to support tumor growth via inhibition of the antitumoral immune response and/or the induction of immunosuppressive cells. In addition, multiple studies have demonstrated that MDSCs provide potential therapeutic targets for the elimination of immunosuppressive functions and the inhibition of tumor growth. The combination of targeting MDSCs and other therapeutic approaches has also demonstrated powerful antitumor effects. In this review, we summarize the characteristics of MDSCs in the tumor microenvironment (TME) and current strategies of cancer treatment by targeting MDSCs.

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Tolerogenic Role of Myeloid Suppressor Cells in Organ Transplantation

Cited by 25 publications

References 85 publications

Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy

Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy

The Engagement Between MDSCs and Metastases: Partners in Crime

Targeting Myeloid-Derived Suppressor Cells in Cancer Immunotherapy

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