Endostatin reverses immunosuppression of the tumor microenvironment in lung carcinoma

Liu,Xiaolin; Nie,Weiwei; Xie,Qi; Chen,Guoling; Li,Xingyu; Jia,Yanrui; Yin,Beibei; Qu,Xun; Li,Yan; Liang,Jing

doi:10.3892/ol.2017.7455

Endostatin reverses immunosuppression of the tumor microenvironment in lung carcinoma

Authors:
- Xiaolin Liu
- Weiwei Nie
- Qi Xie
- Guoling Chen
- Xingyu Li
- Yanrui Jia
- Beibei Yin
- Xun Qu
- Yan Li
- Jing Liang
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Affiliations: Department of Oncology, Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China, Medical Research Center, Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China, Islet Cell Laboratory, MedStar Georgetown University Hospital, Washington, DC 20007, USA, Institute of Basic Medical Sciences and Key Laboratory of Cardiovascular Proteomics of Shandong Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: November 21, 2017 https://doi.org/10.3892/ol.2017.7455
Pages: 1874-1880

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Abstract

Endostatin has previously been demonstrated to efficiently inhibit the angiogenesis and growth of endothelial cells. However, the role of endostatin in the tumor microenvironment remains to be elucidated. To investigate the antitumor effect of endostatin in lung cancer, the present study was designed to explore the alterations of microvessel density in Lewis lung cancer models and the expression of vascular endothelial growth factor (VEGF), interleukin (IL)‑6, IL‑17, interferon (IFN)‑γ and hypoxia inducible factor (HIF)‑1α, following endostatin therapy. It was demonstrated that the growth and angiogenesis of tumors were markedly suppressed by treatment with endostatin, compared with control group. The microvessel density in mice treated with endostatin was significantly inhibited in a dose‑dependent manner. The expression levels of VEGF, IL‑6 and IL‑17 in tumors were decreased, however IFN‑γ and HIF‑1α expression levels were increased, following treatment with endostatin. In addition, the proportion of myeloid derived suppressor cells and tumor associated macrophages (TAMs; M2 type) were significantly decreased, whereas those of mature dendritic cells and TAMs (M1 type) were increased, and cluster of differentiation (CD)8+ T cells were recruited to infiltrate the tumors following treatment with endostatin. In addition, the expression levels of IL‑6, IL‑10, tumor growth factor‑β and IL‑17 in tumor tissue were potently decreased with endostatin therapy. These results indicated that endostatin efficiently inhibited tumor angiogenesis and reversed the immunosuppressive microenvironment associated with the presence of tumors.

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