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LOX-1+ PMN-MDSC enhances immune suppression which promotes glioblastoma multiforme progression

Authors Chai E, Zhang L, Li C

Received 29 March 2019

Accepted for publication 6 June 2019

Published 2 August 2019 Volume 2019:11 Pages 7307—7315

DOI https://doi.org/10.2147/CMAR.S210545

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


ErQing Chai,1,2,* Lan Zhang,3,* Changqing Li4

1Department of Neurosurgery, Gansu Provincial Hospital, Lanzhou 730000, People’s Republic of China; 2Cerebral Vascular Disease Center, Gansu Provincial Hospital, Lanzhou 730000, People’s Republic of China; 3Tuberculosis Prevention and Control Department, Gansu Province Center for Disease Control and Prevention, Lanzhou 730000, People’s Republic of China; 4Neurosurgery Department, Gansu University of Chinese Medicine, Lanzhou 730000, People’s Republic of China

*These authors contributed equally to this work

Background/aims: Patients with glioblastoma multiforme (GBM) that is the most common brain cancer in adults have a rather poor prognosis. The accumulation of immune suppressive myeloid-derived suppressor cell (MDSC) is negatively associated with clinical outcomes in various cancers. A recent study identified that lectin-type oxidized LDL receptor 1 (LOX-1) may serve as a specific marker of human polymorphonuclear neutrophil (PMN)-MDSC. Thus, herein we focused on exploring the role of LOX-1+ PMN-MDSC in GBM progression.
Methods: LOX-1, IFN-γ, dichlorodihydrofluorescein diacetate (DCFDA), CD15, CD4 and CD8 expression levels were examined by flow cytometry. ARG1 and iNOS expression levels in PMN were examined by quantitative real-time PCR. LOX-1 and CD15 expression levels in tumor tissue were determined by immunofluorescent microscopy. T cell proliferation was determined by 3H-thymidine incorporation.
Results: We identified a protumorigenic subset of PMN, which constitutively expressed LOX-1 and accumulated in the peripheral blood of GBM patients. Compared to LOX-1− PMN, the LOX-1+ PMN exhibited a PMN MDSC profile, with a significant increase in the expression of DCFDA, ARG1 and iNOS, and the capacity of inhibiting the CD3+ T cell proliferation in a dependent-ARG1/iNOS way. Additionally, we found that LOX-1+ PMN negatively correlated with effector immune cells in GBM patients, accumulated in GBM tissues, and was related to early recurrence and disease progression tightly.
Conclusion: Our study revealed that LOX-1+ PMN-MDSC inhibited the T cell proliferation to enhance immune suppression, which may play a key role in driving the GBM progression.

Keywords: MDSC, glioblastoma multiforme, immune suppression


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