| Autor: |
Zhong Zheng, Rui Sun, Hui-Jin Zhao, Di Fu, Hui-Juan Zhong, Xiang-Qin Weng, Bin Qu, Yan Zhao, Li Wang, Wei-Li Zhao |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Molecular Cancer, Vol 18, Iss 1, Pp 1-13 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
1476-4598 |
| DOI: |
10.1186/s12943-019-0977-3 |
| Popis: |
Abstract Background MicroRNAs (miRs) are involved in lymphoma progression by regulating tumor cell interaction with microenvironment. MiR155 is overexpressed in diffuse large B-cell lymphoma (DLBCL) and its biological effect on tumor microenvironment needs to be futher investigated. Methods MiR155 was detected by quantitative real-time PCR in patients with newly diagnosed DLBCL. The mechanism of action of miR155 on lymphoma progression and tumor microenvironment was examined in vitro in B-lymphoma cell lines and in vivo in a murine xenograft model. Results Serum miR155 was significantly elevated, correlated with tumor miR155 expression, and indicated poor disease outcome in DLBCL. MiR155 overexpression was associated with decreased peripheral blood CD8+T cells and inhibition of T-cell receptor signaling. Of note, EBV-positive patients showed higher serum miR155 than EBV-negative patients. In co-culture systems of B-lymphoma cells with immune cells, miR155 induced Fas-mediated apoptosis of CD8+T cells, which could be targeted by anti-PD-1 and anti-PD-L1 antibodies. Moreover, miR155 enhanced lymphoma cell PD-L1 expression, recruited CD8+T cells by PD-1/PD-L1 interaction and inhibited CD8+T cell function via dephosphorylating AKT and ERK. MiR155-induced AKT/ERK inactivation was more obvious in CD8+T cells co-cultured with EBV-infected B-lymphoma cells. In vivo in a murine xenograft model established with subcutaneous injection of A20 cells, PD-L1 blockade particularly retarded miR155-overexpressing tumor growth, consistent with maintenance of CD8+T cells and their function. Conclusions As a oncogenic biomarker of B-cell lymphoma, serum miR155 was related to lymphoma progression through modulating PD-1/PD-L1-mediated interaction with CD8+T cells of tumor microenvironment, indicating the sensitivity of B-cell lymphoma to PD-L1 blockade. Also CD8+T cells could be a therapeutic mediator of immune checkpoint inhibitors in treating EBV-associated lymphoid malignancies. |
| Databáze: |
Directory of Open Access Journals |
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