期刊
TRANSLATIONAL ONCOLOGY
卷 40, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2023.101831
关键词
Epstein-Barr virus; Apoptosis; Immune escape; Cancer immunotherapy; B lymphoma
类别
This study demonstrates the significance of PD-1 in EBV-infected lymphoma cells. Silencing PD-1 enhances the tumor targeting effect of EBV-specific killer T cells on B lymphocytes and attenuates the immune escape effect.
Epstein-Barr Virus (EBV) infection is closely associated with the development of lymphoma, as it plays a sig-nificant role in the malignant transformation of lymphocytes. The expression of programmed death-1 (PD-1), which binds to PD-L1 in tumor cells, can lead to immune evasion by lymphoma cells and promote tumor pro-gression. In this study, immortalized B lymphoblastoid cell lines (B-LCLs) positive for EBV-specific proteins were established from human peripheral mononuclear cells (PBMCs) using EBV induction along with CpG-ODN 2006 and cyclosporin A. EBV-specific T cells (EBVST) were generated by multiple immunizations of CD3+ T lym-phocytes using irradiated B-LCLs. Flow cytometry analysis confirmed the activation of EBVST through the detection of CD3+, CD4+, and CD8+ markers. Co-incubation of EBVST with EBV-positive B lymphocyte cell lines resulted in the secretion of perforin by EBVST, leading to granzyme B-mediated cell death and an increase in LDH levels. Silencing PD-1 in EBVST cells enhanced perforin production, increased granzyme B release, and upre-gulated cell death in co-incubated B lymphocytes. In a nude mice tumor transplantation model, silencing PD-1 in combination with EBV-specific killer T cells exhibited the maximum inhibition of B-lymphoblastoma. This treatment upregulated the expression of proteins associated with apoptosis and immune response, while inhibiting anti-apoptotic protein expression in tumor tissues. Silencing PD-1 also increased the infiltration of EBV-specific killer T cells in the tumor tissues. Overall, PD-1 silencing enhanced the tumor targeting effect of EBV-specific killer T cells on EBV-infected B lymphocytes and attenuated the immune escape effect mediated by the PD-1 pathway.
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