Increased circulating <scp>L</scp>in−/low<scp>CD</scp>33+<scp>HLA‐DR</scp>− myeloid‐derived suppressor cells in hepatocellular carcinoma patients

Shen, Peng; Wang, Aijuan; He, Minfei; Wang, Qingqing; Zheng, Shusen

doi:10.1111/hepr.12167

Cited by 63 publications

(51 citation statements)

References 48 publications

(118 reference statements)

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“…It has been reported that MDSCs in peripheral blood are increased in patients with hepatocellular carcinoma2930, and we have similar results in this study. Our data demonstrated that the frequency of PD-L1 + MDSCs increased in HCC patients.…”

Section: Discussionsupporting

confidence: 92%

PD-L1+MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment

Iwata

Kondo

Kimura

et al. 2016

Sci Rep

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Myeloid-derived suppressor cells (MDSCs) could have important roles in immune regulation, and MDSCs can be induced in patients with various malignant tumors. The immune-suppressive functions of MDSCs in hepatocellular carcinoma (HCC) patients have not been clarified. Therefore, we tried to analyze the biological significance of MDSCs in HCC patients. We quantified PD-L1+MDSCs of HCC patients in various conditions by using multi-color flow cytometry analysis. PBMCs from HCC patients contained significantly higher percentages of PD-L1+MDSCs in comparison to those from healthy subjects (p < 0.001). The percentages of PD-L1+MDSCs were reduced by curative treatment for HCC (p < 0.05), and the percentages of PD-L1+MDSCs before treatment were inversely correlated with disease-free survival time. After we cocultivated PBMCs and several liver cancer cell lines in a transwell coculture system, the percentages of PD-L1+MDSCs were significantly increased compared with control (p < 0.05). The expression of M-CSF and VEGFA was higher in the cell lines that strongly induced PD-L1+MDSCs. Peripheral blood from HCC patients had significantly higher percentages of PD-L1+MDSCs in comparison to those of healthy subjects, and the percentages of PD-L1+MDSCs were reduced by HCC treatment, suggesting that we might use PD-L1+MDSCs as a new biomarker of HCC.

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Section: Discussionsupporting

confidence: 92%

PD-L1+MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment

Iwata

Kondo

Kimura

et al. 2016

Sci Rep

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show abstract

“…Neoplastic cells have additional elaborate mechanisms to subvert antitumor T cell activity, for example the induction of host immunosuppressive cells, including MDSCs and regulatory T cells, and MDSCs have been identified in a variety of human malignancies (36). Immunosuppression is not limited to the tumor microenvironment, and circulating myeloid cells capable of inducing dysfunctional immune responses have been repeatedly described (37,38). Therefore, the levels of circulating MDSCs were evaluated, to determine their effect on MAGE-A4 expression.…”

Section: Discussionmentioning

confidence: 99%

Myeloid-derived suppressor cells enhance the expression of melanoma-associated antigen A4 in a Lewis lung cancer murine model

2015

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Abstract. The cancer-testis (CT) family of antigens are expressed in multiple types of malignant neoplasm and are silent in normal tissues, apart from the testis. Immunotherapy targeting CT antigens is a promising therapeutic strategy for treatment of solid tumors. One member of this family, melanoma-associated antigen A4 (MAGE-A4), has been demonstrated to be expressed in melanomas and lung cancer. Patients with tumors expressing the MAGE-A4 antigen exhibit specific cellular and humoral immune responses to the antigen, resulting in a favorable prognosis. Conversely, the expression of MAGE-A4 is associated with poor survival in lung cancer. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells, which are upregulated in the cancer microenvironment. Little is known regarding any potential correlation between the expression of MAGE-A4 antigens and the accumulation of MDSCs. The present study aimed to examine the association between circulating MDSC levels and MAGE-A4 expression in a mouse model of Lewis lung cancer. The expression of MAGE-A4 in tumor cells or tissues was evaluated using western blotting, while the percentage of MDSCs (CD11b + Gr-1 + ) in the blood was detected by flow cytometry. In addition, the suppressive capacity of MDSCs and the effectiveness of MDSC depletion were assessed in C57BL/6 tumor-bearing mice. MDSCs were demonstrated to upregulate MAGE-A4 expression via the phosphosphorylated-signal transducer and activator of transcription 3 705 pathway, while depletion of MDSCs decreased the tumor growth rate, prolonged median survival and enhanced the recognition of MAGE-A4 by CD8 + T cells. These findings indicated that immunotherapeutic strategies involving induction of cytotoxic T lymphocytes that target MAGE-A4, in combination with MDSC depletion, may be an effective approach to immunotherapy for cancer types with high expression of MAGE-A4.

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“…Although the role of MDSCs has been acknowledged in primary tumor formation (119), extensive data connect MDSC expansion to more advanced cancer stages (120). MDSC numbers are associated with clinical stage in bladder carcinoma (121), pancreatic adenocarcinoma (122), hepatocellular carcinoma (123,124), gastric cancer (125), NSCLC (126), and head and neck squamous cell carcinoma (127), as well as in hematological malignancies such as non-Hodgkin lymphoma (128). Collectively, these results indicate that expansion of MDSCs in cancer patients is a general phenomenon accompanying tumor progression.…”

Section: Prognostic Significance Of Myeloid Cells In Cancer Patientsmentioning

confidence: 99%

Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages

Ugel¹,

Sanctis²,

Mandruzzato

et al. 2015

Journal of Clinical Investigation

466

405

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Increased circulating Lin^−/lowCD33⁺HLA‐DR⁻ myeloid‐derived suppressor cells in hepatocellular carcinoma patients

Abstract: Our study provides evidence showing an increased population of Lin(-/low) CD33(+) HLA-DR(-) MDSC in the peripheral blood of HCC patients. Our data also suggest that MMP-13 and COX-2 in PBMC may play a new important role companied with MDSC in HCC patients.

Cited by 63 publications

References 48 publications

PD-L1+MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment

PD-L1+MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment

Myeloid-derived suppressor cells enhance the expression of melanoma-associated antigen A4 in a Lewis lung cancer murine model

Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages

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Increased circulating Lin−/lowCD33+HLA‐DR− myeloid‐derived suppressor cells in hepatocellular carcinoma patients

Abstract: Our study provides evidence showing an increased population of Lin(-/low) CD33(+) HLA-DR(-) MDSC in the peripheral blood of HCC patients. Our data also suggest that MMP-13 and COX-2 in PBMC may play a new important role companied with MDSC in HCC patients.

Cited by 63 publications

References 48 publications

PD-L1+MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment

PD-L1+MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment

Myeloid-derived suppressor cells enhance the expression of melanoma-associated antigen A4 in a Lewis lung cancer murine model

Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages

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Increased circulating Lin^−/lowCD33⁺HLA‐DR⁻ myeloid‐derived suppressor cells in hepatocellular carcinoma patients