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
Checked for plagiarism Yes
Review by Single-blind
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
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]