DC-HIL + CD14 + HLA-DR no/low Cells Are a Potential Blood Marker and Therapeutic Target for Melanoma

Turrentine, Jake E.; Chung, Jane; Nezafati, Kaveh A.; Tamura, Kyoichi; Harker-Murray, Amy; Huth, James F.; Sharma, Rohit; Harker, David; Ariizumi, Kiyoshi; Cruz, Ponciano D.

doi:10.1038/jid.2014.248

Cited by 12 publications

(13 citation statements)

References 12 publications

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“…In a dose-dependent manner, anti-DC-HIL mAb (but not control IgG) incompletely restored T-cell IFN-γ response (up to 63%) that was suppressed by MDSCs. This moderate effect by the mAb was not consistent with data of similar assays using melanoma-derived MDSCs, in which the same mAb reversed the suppressor activity almost completely (Turrentine et al , 2014). DC-HIL-triggered upregulation of nitric oxide (NO) in psoriatic MDSCs showed DC-HIL to be functional (Figure 4b): MDSC of healthy controls did not produce NO (≤0.003 µM) even after stimulation with anti-DC-HIL mAb.…”

Section: Resultscontrasting

confidence: 55%

“…Using these data, we calculated % DC-HIL + MDSCs in total PBMCs and found the population to be expanded significantly in psoriatic blood (4.2%, 0–11% vs. 0.1%, 0.01–0.27%, p <0.001, Figure 1d). This level was higher than in metastatic melanoma patients (2.6 ± 0.6% (Turrentine et al , 2014)). The T-cell ligand SD-4 of DC-HIL was also upregulated in CD4 + and CD8 + T cells of psoriatic patients (Supplementary Figure S2).…”

Section: Resultsmentioning

confidence: 52%

“…Most of the expanded MDSCs expressed DC-HIL and were T-cell suppressors. However, psoriatic MDSCs differ from melanoma MDSCs in 4 aspects; first, psoriatic DC-HIL + MDSCs do not further proliferate with increasing disease severity, unlike those in melanoma that increase in proportion to cancer stages (Turrentine et al , 2014); second, psoriatic DC-HIL + MDCSs are less potent in suppressing T-cell activation compared to melanoma MDSCs; third, their suppressor function is less dependent on DC-HIL; and fourth, they are divergent in the use of inhibitory mediators among patients.…”

Section: Discussionmentioning

confidence: 99%

“…Using mouse models, we showed the DC-HIL/SD-4 pathway to be a potent regulator of T cell-mediated immune responses in contact hypersensitivity, graft-versus-host disease, experimental autoimmune encephalomyelitis (EAE), and melanoma (Chung et al , 2014b; Chung et al , 2013). Recently, we found an expanded MDSC population in melanoma patients express DC-HIL, in which this expression positively correlates with melanoma stage progression; and DC-HIL is a critical mediator of MDSCs’ suppressor function (Turrentine et al , 2014). Thus, DC-HIL may serve as a marker of MDCSs’ immunosuppressive capacity.…”

Section: Introductionmentioning

confidence: 99%

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Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell–Suppressor Mechanisms

Cao

Chung

Teshima

et al. 2016

Journal of Investigative Dermatology

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Psoriasis vulgaris is an inflammatory skin disease caused by hyper-activated T-cells regulated by positive and negative mechanisms; while the former has been much studied, but the latter has not. We studied the regulatory mechanism mediated by myeloid-derived suppressor cells (MDSCs), especially having shown that MDSCs expanded in melanoma patients express DC-HIL, a critical mediator of T-cell suppressor function. We examined expansion of DC-HIL+ MDSCs in psoriasis and characterized their functional properties. Frequency of DC-HIL+ monocytic MDSCs (CD14+HLA-DRno/low) in blood and skin was markedly increased in psoriatic patients vs. healthy controls, but there was no statistically significant relationship with disease severity (PASI score). Blood DC-HIL+ MDSC levels in the untreated patients were significantly higher than the treated patients. Compared to melanoma-derived MDSCs, psoriatic MDSCs exhibited significantly reduced suppressor function, and were less dependent on DC-HIL, but capable of inhibiting proliferation and IFN-γ and IL-17 responses of autologous T-cells. Psoriatic MDSCs were functionally diverse among patients in their ability to suppress allogeneic T-cells and use of either IL-17/arginase I or IFN-γ/iNOS axis as suppressor mechanisms. Thus DC-HIL+ MDSCs are expanded in psoriasis patients, and their mechanistic heterogeneity and relative functional deficiency may contribute to the development of psoriasis.

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Section: Resultscontrasting

confidence: 55%

Section: Resultsmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell–Suppressor Mechanisms

Cao

Chung

Teshima

et al. 2016

Journal of Investigative Dermatology

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“…Psoriasis, a common chronic inflammatory skin disease, is mediated by the pathological cross-talk between epidermal keratinocytes and immune cells [19], including infiltrating CD4 + T cells, CD8 + T cells [20], and Mo-MDSCs [13]. Consistent with other studies [13,21,22], we found increased circulating CD14 + HLA-DR −/low Mo-MDSCs among CD14 + cells in psoriasis patients when compared to healthy controls. Further, circulating Mo-MDSCs were increased in the blood of psoriatic BS syndrome patients and not in patients with BH syndrome.…”

Section: Discussionsupporting

confidence: 90%

Circulating CD14⁺HLA‐DR^−/low Myeloid‐Derived Suppressor Cells as Potential Biomarkers for the Identification of Psoriasis TCM Blood‐Heat Syndrome and Blood‐Stasis Syndrome

Sun

Wei

Zeng

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Psoriasis is a chronic autoimmune disease. Identification of the biomarkers responsible for Traditional Chinese Medicine (TCM) syndromes of psoriasis can help researchers recognize the different aspects of psoriasis and find novel therapeutic targets for the treatment of psoriasis. The current study investigated the levels of circulating Mo-MDSCs and Mo-MDSC-associated immune factors in the peripheral blood of psoriasis patients with different TCM syndromes. We found that the frequency of Mo-MDSCs (CD14+HLA-DR−/low cells) among CD14+ cells from plaque psoriasis patients with blood-stasis (BS) syndrome was significantly increased when compared with healthy controls p<0.001 and blood-heat (BH) syndrome group p<0.001, respectively. However, serum IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, IFN-γ, iNOS, Arg-1, and NO concentration showed no statistically significant difference between healthy controls and psoriasis patients as well as no significant difference between the BH and BS syndrome groups. Compared with healthy controls, the mRNA expression of Arg-1, TNF-α, ROR-γ, and PD-L1 was increased, while the mRNA expression of PD-1 and IL-10 was decreased in PBMCs from psoriasis patients. Moreover, the mRNA expression of TNF-α and FOXP3 in PBMCs showed a pronounced statistical difference between the psoriatic BH syndrome group and the BS syndrome group. Therefore, we provide evidence that the percentage of CD14+HLA-DR−/low MDSC/ CD14+ cells and TNF-α and Foxp3 mRNA expression levels in PBMCs are potential biomarkers for distinguishing TCM BH syndrome and BS syndrome.

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MDSC suppresses T cell antitumor immunity in CAC via GPNMB in a MyD88‐dependent manner

Wang,

Shang

et al. 2023

Cancer Medicine

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BackgroundMyeloid‐derived suppressor cells (MDSCs) played an essential role in tumor microenvironment to suppress host antitumor immunity and help cancer cells escape immune surveillance. However, the molecular mechanism behind tumor evasion mediated by MDSCs is not fully understood. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is considered to associate with tumor initiation, metastasis and angiogenesis. Blocking GPNMB function is a potentially valuable therapy for cancer by eliminating GPNMB+MDSCs. Our previous study has proved that blockage the MyD88 signaling with the MyD88 inhibitor, TJ‐M2010‐5, may completely prevent the development of CAC in mice, accompanying with downregulation of GPNMB mRNA in the inhibitor‐treated mice of CAC.MethodsWe here focus on the underlying the relationship between GPNMB function and MyD88 signaling pathway activation in MDSCs' antitumor activity in CAC.ResultsCAC development in the mouse model is associated with expanded GPNMB+MDSCs by a MyD88‐dependent pathway. The GPNMB expression on MDSCs is associated with MyD88 signaling activation. The inhibitory effect of MDSCs on T cell proliferation, activation and antitumor cytotoxicity in CAC is mediated by GPNMB in a MyD8‐dependent manner.ConclusionMyD88 signaling pathway plays an essential role in GPNMB+MDSC‐mediated tumor immune escape during CAC development and is a promising focus for revealing the mechanisms of MDSC that facilitate immunosuppression and tumor progression.

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DC-HIL + CD14 + HLA-DR no/low Cells Are a Potential Blood Marker and Therapeutic Target for Melanoma

Cited by 12 publications

References 12 publications

Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell–Suppressor Mechanisms

Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell–Suppressor Mechanisms

Circulating CD14⁺HLA‐DR^−/low Myeloid‐Derived Suppressor Cells as Potential Biomarkers for the Identification of Psoriasis TCM Blood‐Heat Syndrome and Blood‐Stasis Syndrome

MDSC suppresses T cell antitumor immunity in CAC via GPNMB in a MyD88‐dependent manner

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DC-HIL + CD14 + HLA-DR no/low Cells Are a Potential Blood Marker and Therapeutic Target for Melanoma

Cited by 12 publications

References 12 publications

Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell–Suppressor Mechanisms

Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell–Suppressor Mechanisms

Circulating CD14+HLA‐DR−/low Myeloid‐Derived Suppressor Cells as Potential Biomarkers for the Identification of Psoriasis TCM Blood‐Heat Syndrome and Blood‐Stasis Syndrome

MDSC suppresses T cell antitumor immunity in CAC via GPNMB in a MyD88‐dependent manner

Contact Info

Product

Resources

About

Circulating CD14⁺HLA‐DR^−/low Myeloid‐Derived Suppressor Cells as Potential Biomarkers for the Identification of Psoriasis TCM Blood‐Heat Syndrome and Blood‐Stasis Syndrome