A novel subset of B7-H3+CD14+HLA-DR−/lowmyeloid-derived suppressor cells are associated with progression of human NSCLC

Zhang, Guangbo; Huang, Haitao; Zhu, Yueyong; Yu, Guangrong; Gao, Xin; Xu, Yunyun; Liu, Cuiping; Hou, Jingli; Zhang, Xueguang

doi:10.4161/2162402x.2014.977164

Cited by 47 publications

(40 citation statements)

References 25 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 .…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…Single cell suspensions of tumor or nontumor sample were obtained after digestion [20]. Briefly, tissues were cut in pieces and placed in petri dishes containing 0.1% Collagenase IV (Invitrogen, Thermo Fisher Scientific Inc., Grand Island, NY, USA) and incubated at 37°C for 60 min.…”

Section: Methodsmentioning

confidence: 99%

TREM-1low is a novel characteristic for tumor-associated macrophages in lung cancer

Zhang

Huang

et al. 2016

Oncotarget

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ObjectiveTo explore the expression feature and biological functions of TREM-1 on tumor-associated macrophages (TAMs) in lung cancer.ResultsThe levels of TREM-1 on tissue-infiltrating monocytes/macrophage from tumor nest were significantly lower than those from nonturmor tissue or peripheral blood samples. Clinical analysis indicated that the levels of TREM-1-related TAMs were significantly decreased during cancer stages progression. The tumor-bearing mouse model further confirmed that the expression of TREM-1 on TAMs was significantly decreased with tumor growth. In addition, we found the activation of TREM-1 could significantly enhance the secretion of IL-1β by TAM in vitro. Furthermore, T-bet but not Eomes was found to be the key transcription factor for the TREM-1 expression on monocytes/macrophage.MethodsA total of 40 patients with non-small cell lung cancer (NSCLC) were enrolled in this study. The expression characteristics of TREM-1 in blood and tissue-infiltrating monocytes/macrophage were examined by flow cytometry analysis. After the treatment of TREM-1 antibody, which is an agonist of TREM-1, cytokines secreted by TAM were then analyzed. In LLC-tumor bearing mouse model, we further investigated the dynamic expression feature of TREM-1 on macrophage with tumor growth. Moreover, we explored the transcription factor for regulating TREM-1 expression on monocyes/macrophage with wildtype, T-bet Ko or Eomes Ko mice.ConclusionThe levels of TREM-1 were remarkably decreased during tumor progression. The low expression level of TREM-1 might be a characteristic for TAMs in lung cancer.

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“…The proliferation and aggregation of MDSCs in human malignant neoplasms may have an effect on tumor progression and prognosis. The definition of these immunosuppressive cells in patients is problematical, since there is no human homolog of Gr-1 marker, and no correlation between phenotype and immune suppressive properties has been reported (11,24). Identifying MDSCs may aid in developing anticancer treatments that target these cell populations.…”

Section: Discussionmentioning

confidence: 99%

“…Multicolor fluorescence-activated cell sorting (FACS) analysis was performed using the following antibodies: Anti-CD14 (560634, 20 µg/ml), anti-HLA-DR-PerCp (552764, 10 µg/ml), anti-CD3-APC (565119, 5 µg/ml), anti-CD4-PE (562281, 20 µg/ml) and anti-CD8-FITC (555366, 20 µg/ml), all supplied by BD Pharmingen, San Diego, CA, USA. Flow cytometry was performed using a FACS Calibur™ flow cytometer (BD Biosciences), according to a previously descibed method (11). Analysis of the FACS data was performed using FlowJo software (version X.0.7; TreeStar, Inc., Ashland, OR, USA).…”

Section: Fl Ow C Yto M Et R Yto D Eter M I N E T H E F Requ E N C Y Omentioning

confidence: 99%

Functional analysis of CD14+HLA-DR−/low myeloid-derived suppressor cells in patients with lung squamous cell carcinoma

et al. 2017

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A novel subset of B7-H3⁺CD14⁺HLA-DR^−/lowmyeloid-derived suppressor cells are associated with progression of human NSCLC

Cited by 47 publications

References 25 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

TREM-1low is a novel characteristic for tumor-associated macrophages in lung cancer

Functional analysis of CD14+HLA-DR−/low myeloid-derived suppressor cells in patients with lung squamous cell carcinoma

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