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NSE from diffuse large B-cell lymphoma cells regulates macrophage polarization

Authors Zhu MY, Liu WJ, Wang H, Wang WD, Liu NW, Lu Y

Received 26 January 2019

Accepted for publication 20 April 2019

Published 17 May 2019 Volume 2019:11 Pages 4577—4595


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Nakshatri

Meng-yuan Zhu,1–3,* Wen-jian Liu,1,2,* Hua Wang,1,2,* Wei-da Wang,1,2 Na-wei Liu,1,2 Yue Lu1,2

1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 2Department of Hematological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 3Department of Oncology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, People’s Republic of China

*These authors contributed equally to this work

Diffuse large B-cell lymphoma (DLBCL) is a highly common type of malignant and heterogeneous non-Hodgkin’s lymphoma. Tumor-associated macrophages, specially the M2-type, promote tumor progression and drug resistance. The clinical outcome of patients with high neuron-specific enolase (NSE) expression is worse than that with low NSE expression. The tumor-promoting mechanism of NSE, however, remains unclear. This study explored the role of NSE in macrophage polarization associated with the immune microenvironment of DLBCL.
Results: Our results showed that NSE protein expression was higher in lymphoma cell lines than in the B lymphocytes. Functional studies demonstrated that upregulation of NSE in lymphoma cells could promote M2 polarization and migration ability of macrophage, thereby consequently promoting the progression of lymphoma in vitro and in vivo. Further mechanism studies revealed that lymphoma-derived exosomes could mediate NSE into macrophages, NSE enhanced nuclear p50 translocation with subsequent defective classical nuclear factor-κB activity in macrophages.
Conclusions: These results indicate that NSE may be a potential target for lymphoma therapy and a prognosis marker for lymphoma.

Keywords: neuron-specific enolase, diffuse large B-cell lymphoma, macrophage

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