PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma In Vitro
| Autor: | Xiuchen Guo, Yue Liu, Xue Chen, Aichun Liu, Shujie Yan, Lina Quan, Yan Zhang |
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| Rok vydání: | 2015 |
| Předmět: |
Epstein-Barr Virus Infections
Herpesvirus 4 Human T-Lymphocytes Programmed Cell Death 1 Receptor lcsh:Medicine Gene Expression Biology Lymphocyte Activation Immune system T-Lymphocyte Subsets immune system diseases Cell Line Tumor hemic and lymphatic diseases Tumor Microenvironment medicine Humans Cytotoxic T cell lcsh:Science neoplasms Epstein–Barr virus infection Aged Cell Line Transformed Neoplasm Staging Aged 80 and over Tumor microenvironment Multidisciplinary lcsh:R Germinal center Middle Aged medicine.disease Blockade Lymphoma Phenotype Case-Control Studies Immunology Cytokines lcsh:Q Lymphoma Large B-Cell Diffuse Lymphocyte Culture Test Mixed Immunologic Memory Diffuse large B-cell lymphoma Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 9, p e0136476 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) is an aggressive malignancy that is largely resistant to current therapeutic regimens, and is an attractive target for immune-based therapies. Anti-programmed death-1 (PD-1) antibodies showed encouraging anti-tumor effects in both preclinical models and advanced solid and hematological malignancies, but its efficacy against EBV+DLBCL is unknown. Herein, we performed experiments using co-culture system with T cells and lymphoma cell lines including EBV+DLBCL and EBV-DLBCL [including germinal center B-cell like (GCB)-DLBCL and non-GCB-DLBCL] in vitro. We show that lymphoma cells augmented the expression of PD-1 on T cells, decreased the proliferation of T cells, and altered the secretion of multiple cytokines. However, through PD-1 blockade, these functions could be largely restored. Notbaly, the effect of PD-1 blockade on antitumor immunity was more effective in EBV+DLBCL than that in EBV-DLBCL in vitro. These results suggest that T-cell exhaustion and immune escape in microenvironment is one of the mechanisms underlying DLBCL; and PD-1 blockade could present as a efficacious immunotherapeutic treatment for EBV+DLBCL. |
| Databáze: | OpenAIRE |
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