Increased circulating CD14(+)HLA-DR-/low myeloid-derived suppressor cells are associated with poor prognosis in patients with small-cell lung cancer

Tian, Tian; Gu, Xiaobin; Zhang, Bo; Liu, Yang; Yuan, Chao; Shao, Lijuan; Guo, Yajun; Fan, Kexing

doi:10.3233/cbm-150473

Cited by 52 publications

(28 citation statements)

References 20 publications

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“…Immature myeloid cells, including MDSCs and TAMs, are essential components of the tumour stroma which are deeply intertwined in the course of tumour development and tumour recurrence and have emerged as key immune modulators that suppress antitumour immune responses through a variety of mechanisms . Clinical studies have also demonstrated that MDSCs are critical tumour‐promoting immune cells correlating with poor clinical outcome, including tumour metastasis and survival . Our previous study revealed that the accumulation of MDSCs and TAMs significantly associated with activation of immune checkpoint molecule PD‐1 , CTLA‐4 and B7‐H4 .…”

Section: Discussionmentioning

confidence: 94%

Selective blockade of B7‐H3 enhances antitumour immune activity by reducing immature myeloid cells in head and neck squamous cell carcinoma

Mao

Fan

et al. 2017

J Cellular Molecular Medi

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Immature myeloid cells including myeloid‐derived suppressor cells (MDSCs) and tumour‐associated macrophages (TAMs) promote tumour growth and metastasis by facilitating tumour transformation and angiogenesis, as well as by suppressing antitumour effector immune responses. Therefore, strategies designed to reduce MDSCs and TAMs accumulation and their activities are potentially valuable therapeutic goals. In this study, we show that negative immune checkpoint molecule B7‐H3 is significantly overexpressed in human head and neck squamous cell carcinoma (HNSCC) specimen as compared with normal oral mucosa. Using immunocompetent transgenic HNSCC models, we observed that targeting inhibition of B7‐H3 reduced tumour size. Flow cytometry analysis revealed that targeting inhibition of B7‐H3 increases antitumour immune response by decreasing immunosuppressive cells and promoting cytotoxic T cell activation in both tumour microenvironment and macroenvironment. Our study provides direct in vivo evidence for a rationale for B7‐H3 blockade as a future therapeutic strategy to treat patients with HNSCC.

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Section: Discussionmentioning

confidence: 94%

Selective blockade of B7‐H3 enhances antitumour immune activity by reducing immature myeloid cells in head and neck squamous cell carcinoma

Mao

Fan

et al. 2017

J Cellular Molecular Medi

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“…MDSCs are a heterogeneous population of cells with a marked ability to suppress T cell responses 24 and are considered an indicator of poor prognosis in some cancers. 25,26 Tregs are a subpopulation of suppressor T cells that generally suppress or downregulate the induction and proliferation of effector T cells. 27 OVs can effectively The heatmap shows the expression of immune signatures containing 681 immune-related genes in bilateral tumors.…”

Section: Discussionmentioning

confidence: 99%

oHSV2 Can Target Murine Colon Carcinoma by Altering the Immune Status of the Tumor Microenvironment and Inducing Antitumor Immunity

Zhang

Liang

et al. 2020

Molecular Therapy - Oncolytics

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Oncolytic viruses are promising immunoreagents. Numerous studies have shown that oncolytic virotherapy is effective for many tumors. Herein, we investigated the therapeutic effect of oHSV2, an oncolytic type 2 herpes simplex virus, on mouse colon carcinoma. The in vivo antitumor efficacy of oHSV2 was observed in both unilateral and bilateral colon cancer models. oHSV2 effectively eliminated tumors and prolonged the survival of mice without side effects. Additionally, treatment with oHSV2 effectively prevented the growth of rechallenged tumors and distant implanted tumors. The specific killing ability of splenic immune cells to tumor cells was enhanced. oHSV2 treatment effectively reduced the content of inhibitory immune cells (regulatory T cells [Tregs] and myeloid-derived suppressor cells [MDSCs]) and increased the content of positive immune cells (natural killer [NK], CD8 + T, and dendritic cells [DCs]) in the spleen. Moreover, treatment with oHSV2 remodeled the tumor immune microenvironment. In summary, treatment with oHSV2 can effectively eliminate primary tumors, generate tumor-specific immunity, and elicit immune memory to inhibit tumor recurrence and metastasis. Furthermore, this virotherapy can reshape the immune status of the spleen and tumor microenvironment in mice, which can further improve the therapeutic antitumor effect.

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“…However, there are still no uniform standards for surface molecular markers of human MDSCs, and many other markers are being reported gradually. From the perspective of LC, according to multicolor immunofluorescence staining evaluated by fluorescenceactivated cell sorting (FACS), the following phenotypes of MDSCs have been reported (shown in Table 1): CD11b + CD14 − CD15 + CD33 + [14], CD11b + CD14 + S100A9 + [15], CD16 low CD11b + CD14 − HLA-DR − CD15 + CD33 + [16], CD14 + HLA-DR −/low [17,18], B7-H3 + CD14 + HLA-DR −/low [19], CD11b + CD14 − HLA-DR − CD33 + CD15 + ILT3 high [20], Lin − CD14 − CD11b + CD39 + CD73 + [21], Lin − CD14 + CD11b + C D39 + CD73 + [21], Lin − CD14 + CD15 + H LA-DR − [22], Lin − C D14 + CD15 − HLA-DR − [22], Lin − CD14 − HLA-DR − [22], Lin-CD33 + CD14 + CD15 − HLA-DR − [25], CD33 + CD11b + CD14 − [27], CD33 + CD11b + CD14 + HLA-DR −/low [27], and CCR 5 + HLA-DR −/low CD11b + CD14 + CD15 − [28].…”

Section: Main Phenotypic and Functional Characteristics Of Mdscsmentioning

confidence: 99%

“…These suppressive cells upregulated the expression of gp91 phox , an important component of the ROS-generating enzyme NADPH oxidase [17]. Subsequently, for small cell lung cancer (SCLC) patients, the frequency of CD14 + HLA-DR −/low MDSCs was also found to be negatively correlated with clinical outcomes [18]. Zhang et al identified a new subset of MDSCs in the tumor microenvironment of NSCLC, B7-H3 + CD14 + HLA-DR −/low MDSCs (B7-H3 + MDSCs).…”

Section: Role Of Mdscs In the Development Of Lcmentioning

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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Increased circulating CD14(+)HLA-DR-/low myeloid-derived suppressor cells are associated with poor prognosis in patients with small-cell lung cancer

Abstract: The frequency of CD14(+)HLA-DR-/low MDSCs could be considered as a poor prognostic predictor in SCLC and the elimination of MDSCs during medical interventions may improve the prognosis of SCLC patients.

Cited by 52 publications

References 20 publications

Selective blockade of B7‐H3 enhances antitumour immune activity by reducing immature myeloid cells in head and neck squamous cell carcinoma

Selective blockade of B7‐H3 enhances antitumour immune activity by reducing immature myeloid cells in head and neck squamous cell carcinoma

oHSV2 Can Target Murine Colon Carcinoma by Altering the Immune Status of the Tumor Microenvironment and Inducing Antitumor Immunity

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

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