Monocyte-Derived Suppressor Cells in Transplantation

Ochando, Jordi; Conde, P.; Bronte, Vincenzo

doi:10.1007/s40472-015-0054-9

Cited by 26 publications

(18 citation statements)

References 51 publications

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“…Recent evidence suggests that macrophages are also important during the induction of transplantation tolerance (5). Presence of graft infiltrating macrophages has been described in long-term surviving transplant recipients and these immunosuppressive macrophages are associated with unresponsiveness to the transplanted organ (6). These suppressive macrophages are characterized phenotypically by their low expression of Ly6C (Ly6C lo or M2) (5).…”

Section: Introductionmentioning

confidence: 99%

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

Braza

Conde

Garcia

et al. 2018

American Journal of Transplantation

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Summary The colony-stimulating factor 1 (CSF1) regulates the differentiation and function of tissue macrophages and determines the outcome of the immune response. The molecular mechanisms behind CSF1-mediated macrophage development remain to be elucidated. Here we demonstrate that neutrophil-derived CSF1 controls macrophage polarization and proliferation, which is necessary for the induction of tolerance. Inhibiting neutrophil production of CSF1 or preventing macrophage proliferation, using targeted nanoparticles loaded with the cell cycle inhibitor simvastatin, abrogates the induction of tolerance. These results provide new mechanistic insights into the developmental requirements of tolerogenic macrophages and identify CSF1 producing neutrophils as critical regulators of the immunological response.

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Section: Introductionmentioning

confidence: 99%

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

Braza

Conde

Garcia

et al. 2018

American Journal of Transplantation

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“…The observations include a demonstrated increase in both the number and activity of effector T and NK cells along with elevated HLA-DR expression, consistent with other studies 76–78 . These findings suggest that MDSC expansion exists as a counter-regulatory mechanism elicited by certain anti-myeloma agents, and suggests concomitant MDSC suppression could be an important strategy to prevent relapse after autologous stem cell transplant and chemoimmunotherapy 79 . Interestingly, dexamethasone potentiates MDSC immunosuppressive effects 80,81 which is considered a mechanism of action for glucocorticoids in the allograft setting 82 .…”

Section: Role Of Mdscs In the Tumor-induced Immunosuppressive Networkmentioning

confidence: 86%

Myeloid-derived suppressor cells: The green light for myeloma immune escape

et al. 2016

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Myeloid-derived suppressor cells (MDSCs) are a heterogeneous, immature myeloid cell population with the ability to suppress innate and adaptive immune responses that promote tumor growth. MDSCs are increased in patients with multiple myeloma (MM) and have bidirectional interaction with tumors within the MM microenvironment. MM-MDSCs promote MM tumor growth and induce immune suppression; conversely, MM cells induce MDSC development and survival. Although the role of MDSCs in infections, inflammatory diseases and solid tumors has been extensively characterized, their tumor-promoting and immune-suppressive role in MM and the MM microenvironment is only beginning to emerge. The presence and activation of MDSCs in MM patients has been well documented; however, the direct actions and functional consequences of MDSCs on cancer cells is poorly defined. Immunosuppressive MDSCs play an important role in tumor progression primarily because of their capability to promote immune-escape, angiogenesis, drug resistance and metastasis. However, their role in the bone marrow (BM), the primary MM site, is poorly understood. MM remains an incurable malignancy, and it is likely that the BM microenvironment protects MM against chemotherapy agents and the host immune system. A growing body of evidence suggests that host immune cells with a suppressive phenotype contribute to a myeloma immunosuppressive network. Among the known suppressor cells, MDSCs and T regulatory cells (Tregs) have been found to be significantly increased in myeloma patients and their levels correlate with disease stage and clinical outcome. Furthermore, it has been shown that MDSC can mediate suppression of myeloma-specific T-cell responses through the induction of T-cell anergy and Treg development in the MM microenvironment. Here, we review clinical correlations and the preclinical proof-of-principle data on the role of MDSCs in myeloma immunotolerance and highlight the mechanistically relevant MDSC-targeted compounds and their potential utility in a new approach for anti-myeloma therapy.

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“…(32,33) In our study, we found that regulatory CD4T cells or CD8T cells preferentially resided in the liver rather than in any other tissues including the spleen, lymph node, or PBMC. Interestingly, MDSCs which are known as suppressive regulators of the immune responses, (34) also resided in high numbers in the liver when compared with the spleen, lymph node, and PBMC.…”

Section: Discussionmentioning

confidence: 99%

Memory T cells are significantly increased in rejected liver allografts of rhesus monkeys

Kim

Lee

et al. 2018

Liver Transpl

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The rhesus monkey (RM) is an excellent preclinical model in kidney, heart, and islet transplantation that has provided the basis for new immunosuppressive protocols for clinical studies. However, there remain relatively few liver transplantation (LT) models in nonhuman primates. In this study, we analyzed the immune cell populations of peripheral blood mononuclear cells (PBMCs) and secondary lymphoid organs along with livers of normal RMs and compared them with those of rejected LT recipients following withdrawal of immunosuppression. We undertook 5 allogeneic ABO compatible orthotopic LTs in monkeys using 5 normal donor monkey livers. We collected tissues including lymph nodes, spleens, blood, and recipient livers, and we performed flow cytometric analysis using isolated immune cells. We found that CD4 or CD8 naïve T cells were normally seen at low levels, and memory T cells were seen at high levels in the liver rather than lymphoid organs or PBMC. However, regulatory cells such as CD4+ forkhead box P3+ T cells and CD8+ CD28– cells remained in high numbers in the liver, but not in the lymph nodes or PBMC. The comparison of CD4/8 T subpopulations in normal and rejected livers and the various tissues showed that naïve cells were dramatically decreased in the spleen, lymph node, and PBMCs of rejected LT monkeys, but rather, the memory CD4/8 T cells were increased in all tissues and PBMC. The normal liver has large numbers of CD4 regulatory T cells, CD8+ CD28–, and myeloid‐derived suppressor cells, which are known immunosuppressive cells occurring at much higher levels than those seen in lymph node or peripheral blood. Memory T cells are dramatically increased in rejected liver allografts of RMs compared with those seen in normal RM tissues. Liver Transplantation 24 256–268 2018 AASLD.

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Monocyte-Derived Suppressor Cells in Transplantation

Cited by 26 publications

References 51 publications

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

Myeloid-derived suppressor cells: The green light for myeloma immune escape

Memory T cells are significantly increased in rejected liver allografts of rhesus monkeys

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