The biology of myeloid‐derived suppressor cells: The blessing and the curse of morphological and functional heterogeneity

Youn, Jang H.; Gabrilovich, Dmitry I.

doi:10.1002/eji.201040895

Cited by 516 publications

(508 citation statements)

References 55 publications

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“…88 MDSCs are classically distinguished between Monocytic (Mo-MDSCs) and Granulocytic (G-MDSCs) subsets based on morphological and phenotypical aspects. 88 Peripheral blood MDSC levels were higher in patients with ATC compared to healthy controls and correlated with the serum level of IL-10, thus suggesting a correlation between MDSCs and systemic immunosuppression. 89 The only study investigating the significance of TC-infiltrating MDSCs failed to find an association between MDSC density and patient survival.…”

Section: Mdscs: Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

The immune network in thyroid cancer

2016

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The immune system plays critical roles in tumor prevention, but also in its initiation and progression. Tumors are subjected to immunosurveillance, but cancer cells generate an immunosuppressive microenvironment that favors their escape from immune-mediated elimination. During chronic inflammation, immune cells can contribute to the formation and progression of tumors by producing mitogenic, prosurvival, proangiogenic and lymphangiogenic factors. Thyroid cancer is the most frequent type of endocrine neoplasia and is the most rapidly increasing cancer in the US. In this review, we discuss recent findings on how different immune cells and mediators can contribute to thyroid cancer development and progression.

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Section: Mdscs: Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

The immune network in thyroid cancer

2016

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“…MDSCs constitute one of the major populations of immune cells capable of regulating antitumor immune responses (40). In addi- (E-G) Six days after tumor challenge, tumors and TDLNs were collected and the expression of CD86 on DCs (defined as CD3 2 NKp46 2 B220 2 CD11c + ) was evaluated by flow cytometry (E), the relative abundance of IFN-b transcripts was evaluated by qPCR (F), and the frequency of DCs was evaluated by flow cytometry.…”

Section: Nk Cells Limit DC Maturation Without Affecting Other Regulatmentioning

confidence: 99%

NK Cells Restrain Spontaneous Antitumor CD8+ T Cell Priming through PD-1/PD-L1 Interactions with Dendritic Cells

Iraolagoitia

Spallanzani

Torres

et al. 2016

The Journal of Immunology

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Despite the classical function of NK cells in the elimination of tumor and of virus-infected cells, evidence for a regulatory role for NK cells has been emerging in different models of autoimmunity, transplantation, and viral infections. However, this role has not been fully explored in the context of a growing tumor. In this article, we show that NK cells can limit spontaneous cross-priming of tumor Ag-specific CD8+ T cells, leading to reduced memory responses. After challenge with MC57 cells transduced to express the model Ag SIY (MC57.SIY), NK cell–depleted mice exhibited a significantly higher frequency of SIY-specific CD8+ T cells, with enhanced IFN-γ production and cytotoxic capability. Depletion of NK cells resulted in a CD8+ T cell population skewed toward an effector memory T phenotype that was associated with enhanced recall responses and delayed tumor growth after a secondary tumor challenge with B16.SIY cells. Dendritic cells (DCs) from NK cell–depleted tumor-bearing mice exhibited a more mature phenotype. Interestingly, tumor-infiltrating and tumor-draining lymph node NK cells displayed an upregulated expression of the inhibitory molecule programmed death ligand 1 that, through interaction with programmed death-1 expressed on DCs, limited DC activation, explaining their reduced ability to induce tumor-specific CD8+ T cell priming. Our results suggest that NK cells can, in certain contexts, have an inhibitory effect on antitumor immunity, a finding with implications for immunotherapy in the clinic.

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“…Several factors have been involved into the generation and functionality of MDSCs, particularly arginase, Signal Transducer and Activator of Transcription 3 (STAT3), indoleamine 2,3-dioxygenase (IDO), reactive oxygen species and others. 18,19 As previous studies found that ECP enhances arginase I mRNA expression and enzyme activity in GvHD patients, 31 we focused on this pathway in our study. Our analyses demonstrated that ECP treatment increased arginase I activity both extracellularly in serum and intracellularly in the PMN-MDSC-containing PBMC fraction in GvHD patients, with PMN-MDSCs showing tendentially higher arginase I activity compared with autologous PBMCs (Figure 2c and Supplementary Figure 7).…”

Section: Neutrophilic Mdscs Functionally Suppress T-cell Responsesmentioning

confidence: 99%

“…17 Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell population characterized by their capacity to potently suppress T-cell proliferation and T-cell cytokine responses. 18,19 Although MDSCs have been initially reported to have a role in cancer, an emerging body of evidence suggests that MDSCs are induced in a broad variety of chronic inflammatory disease conditions as an intrinsic anti-inflammatory mechanism induced to dampen excessive T-cell activities. 20 Functionally, MDSCs are comparable to Tregs, but can be characterized and isolated based on surface marker expression profiles.…”

Section: Introductionmentioning

confidence: 99%

Extracorporeal photopheresis increases neutrophilic myeloid-derived suppressor cells in patients with GvHD

Rieber

Wecker

Neri

et al. 2014

Bone Marrow Transplant

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Extracorporeal photopheresis (ECP) is beneficial in patients with T-cell-mediated disorders, including GvHD, but the underlying immunological mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterized by their capacity to suppress T-cell proliferation. We quantified MDSCs by flow cytometry in peripheral blood from patients after BMT with GvHD before and after ECP treatment, patients after BMT but without GvHD and age-matched healthy controls. MDSC functionality was analyzed using T-cell proliferation, cytokine release and arginase activity. GvHD patients showed increased baseline percentages of neutrophilic MDSCs (PMN-MDSCs) compared with healthy controls and patients after BMT without GvHD. ECP treatment in GvHD patients rapidly increased circulating percentages of PMN-MDSCs. Functionally, PMN-MDSCs efficiently dampened Th1 and Th17 responses and were paralleled by an increase of cellular and extracellular arginase activity. Following ECP longitudinally over 16 weeks, two GvHD responder subgroups were identified, with group one continuously increasing PMN-MDSCs and group two with stable or decreasing PMN-MDSCs over time. This study demonstrates for the first time that ECP increases T-cell-dampening PMN-MDSCs in GvHD patients, a finding that should be confirmed in larger series of GvHD patients.

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The biology of myeloid‐derived suppressor cells: The blessing and the curse of morphological and functional heterogeneity

Cited by 516 publications

References 55 publications

The immune network in thyroid cancer

The immune network in thyroid cancer

NK Cells Restrain Spontaneous Antitumor CD8+ T Cell Priming through PD-1/PD-L1 Interactions with Dendritic Cells

Extracorporeal photopheresis increases neutrophilic myeloid-derived suppressor cells in patients with GvHD

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