Myeloid‐derived suppressor cells: Important contributors to tumor progression and metastasis

Safarzadeh, Elham; Orangi, Mona; Mohammadi, Hamed; Babaie, Farhad; Baradaran, Behzad

doi:10.1002/jcp.26075

Cited by 151 publications

(121 citation statements)

References 145 publications

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“…23,24 In addition, significant expansion of MDSCs in peripheral blood has been reported in patients with multiple myeloma, non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. 25-27 However studies on the contributions of MDSCs to the pathogenesis of AML are scarce. One report showed a significant increase of MDSCs in the bone marrow of AML patients at initial diagnosis and an association of high MDSCs with minimal residual disease.…”

Section: Discussionmentioning

confidence: 99%

VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML

et al. 2018

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Treatment of acute myeloid leukemia (AML) remains challenging. Enhancement of anti-tumor responses by blocking negative immune regulators is a promising strategy for novel effective leukemia therapeutics. V-domain Ig suppressor of T-cell activation (VISTA) is a recently defined negative regulator mediating immune evasion in cancer. To investigate the effect of VISTA on anti-leukemia immune response in AML, we initiated a study using clinical samples collected from AML patients. Here we report that VISTA is highly expressed on myeloid-derived suppressor cells (MDSCs) in the peripheral blood of AML patients. Both the frequency and intensity of VISTA expression on MDSCs are significantly higher in newly diagnosed AML than in healthy controls. Importantly knockdown of VISTA by specific siRNA potently reduced the MDSCs-mediated inhibition of CD8 T cell activity in AML, suggesting a suppressive effect of VISTA on anti-leukemia T cell response. Furthermore, we observed a strong positive association between MDSC expression of VISTA and T cell expression of PD-1 in AML. These results support the strategy of VISTA-targeted treatment for AML and underscore the strong potential for combined blockade of VISTA and PD-1 pathways in effective leukemia control.

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Section: Discussionmentioning

confidence: 99%

VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML

et al. 2018

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“…But, under pathological conditions such as cancer, they are arrested in their differentiation, resulting in the accumulation of MDSC. Increasing evidence indicates that MDSC not only provide evasion of tumor immunity but also augment the metastatic potential of tumor cells through promoting pre‐metastatic niche formation . Indeed, CXCR2 signaling is reported be responsible for the accumulation of MDSC in PDAC, and blockade of CXCR2 signaling contributes to improved tumor immunity and reduced metastasis of PDAC in mice .…”

Section: Discussionmentioning

confidence: 99%

Vasohibin‐2 plays an essential role in metastasis of pancreatic ductal adenocarcinoma

et al. 2019

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Vasohibin‐2 (VASH2) is expressed in various cancers and promotes their progression. We recently reported that pancreatic cancer patients with higher VASH2 expression show poorer prognosis. Herein, we sought to characterize the role of VASH2 in pancreatic cancer. We used LSL‐KrasG12D; LSL‐Trp53R172H; Pdx‐1‐Cre (KPC) mice, a mouse model of pancreatic ductal adenocarcinoma (PDAC), and cells isolated from them (KPC cells). Knockdown of Vash2 from PDAC cells did not affect their proliferation, but decreased their migration. When Vash2‐knockdown PDAC cells were orthotopically inoculated, liver metastasis and peritoneal dissemination were reduced, and the survival period was significantly prolonged. When KPC mice were crossed with Vash2‐deficient mice, metastasis was significantly decreased in Vash2‐deficient KPC mice. VASH2 was recently identified to have tubulin carboxypeptidase activity. VASH2 knockdown decreased, whereas VASH2 overexpression increased tubulin detyrosination of PDAC cells, and tubulin carboxypeptidase (TCP) inhibitor parthenolide inhibited VASH2‐induced cell migration. We next clarified its role in the tumor microenvironment. Tumor angiogenesis was significantly abrogated in vivo when VASH2 was knocked down or deleted. We further examined genes downregulated by Vash2 knockdown in KPC cells, and found chemokines and cytokines that were responsible for the recruitment of myeloid derived suppressor cells (MDSC). Indeed, MDSC were accumulated in PDAC of KPC mice, and they were significantly decreased in Vash2‐deficient KPC mice. These findings suggest that VASH2 plays an essential role in the metastasis of PDAC with multiple effects on both cancer cells and the tumor microenvironment, including tubulin detyrosination, tumor angiogenesis and evasion of tumor immunity.

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“…Moreover, PMN-MDSCs have relatively moderate suppressive activity and play a major role in the regulation of tumor-specific immune responses, ultimately leading to the development of tumor-specific T cell tolerance. In tumor tissue, MDSCs have relatively strong suppressive functions, and M-MDSCs account for a greater proportion and more suppression than PMN-MDSCs and can rapidly differentiate into TAMs and DCs [37]. These findings suggest that targeting only one branch of myeloid cells (monocytes and/or Mø or granulocytes) or only intratumoral populations will not be sufficient for achieving therapeutic benefits.…”

Section: Main Phenotypic and Functional Characteristics Of Mdscsmentioning

confidence: 99%

Myeloid-derived suppressor cells—new and exciting players in lung cancer

et al. 2020

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Lung cancer (LC) is the leading cause of cancer-related death worldwide due to its late diagnosis and poor outcomes. As has been found for other types of tumors, there is increasing evidence that myeloid-derived suppressor cells (MDSCs) play important roles in the promotion and progression of LC. Here, we briefly introduce the definition of MDSCs and their immunosuppressive functions. We next specifically discuss the multiple roles of MDSCs in the lung tumor microenvironment, including those in tumor growth and progression mediated by inhibiting antitumor immunity, and the associations of MDSCs with a poor prognosis and increased resistance to chemotherapy and immunotherapy. Finally, we also discuss preclinical and clinical treatment strategies targeting MDSCs, which may have the potential to enhance the efficacy of immunotherapy.

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Myeloid‐derived suppressor cells: Important contributors to tumor progression and metastasis

Cited by 151 publications

References 145 publications

VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML

VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML

Vasohibin‐2 plays an essential role in metastasis of pancreatic ductal adenocarcinoma

Myeloid-derived suppressor cells—new and exciting players in lung cancer

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