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

Abstract

Background/aims: 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

Acknowledgments

This study was supported by the National Natural Science Foundation of China (contract/grant number: 81272620), Science and Technology Projects of Guangdong Province (contract/grant numbers: 2014A020212577), and Medical Research Foundation of Guangdong Province (contract/grant number: A2015008). The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn), with the approval RDD number as RDDB2018000504.

Disclosure

The authors report no conflicts of interest in this work.

Supplementary materials

Figure S1 NSE from lymphoma cells did not affect the expression of M1 polarization markers. (A) THP-1 cells were co-cultured with different lymphoma cells for 72 hrs and then the M1 phenotype marker mRNA levels of CD86, IL-12p40, and TNF-α were analyzed using RT-qPCR and statistically analyzed. Data were shown as the mean ± SD (n=3), ns P>0.05. (B1) and (B2) Expression levels of CD68+ CD86+ cells in xenografts tissues were quantified through double immunohistofluorescence. Data were shown as the mean ± SD (n=4). ns P>0.05.

Figure S2 Change of NSE levels did not affect the growth of lymphoma cells. (A) Proliferation of OCI-LY1 and SU-DHL-2 sublines was analyzed by EdU. (B) Apoptosis of OCI-LY1 and SU-DHL-2 sublines were analyzed by AnnexinV PE/7AAD. (C) Cell viability of OCI-LY1 and SU-DHL-2 sublines was analyzed by CCK8 assay. Data were shown as the mean ± SD (n=3). ns P>0.05.