HKBU biologist studies the mechanism of Epstein-Barr Virus (EBV) in γδ T cell-mediated cytotoxicity towards nasopharyngeal cancer cells
2023.1.27
Historically, the treatment of nasopharyngeal carcinoma has been based on mainly radiotherapy, chemotherapy, and surgery, but they have significant side effects, limited effectiveness, and a high recurrence rate. Therefore, the search for new treatments is imminent. In recent years, immunotherapy has become increasingly promising, and it also plays an essential role in treating nasopharyngeal carcinoma. Recently, the research team composed of Dr Allen KL Cheung, Department of Biology, Dr Hong-lok Lung and Professor Ka-Leung Wong, Department of Chemistry, of Hong Kong Baptist University, and Professor Yoshimasa Tanaka of Nagasaki University revealed that EBV membrane protein LMP1 plays a vital role in mediating the killing of nasopharyngeal cancer cells by adoptively transferred Vδ 2 T cells, which shed light on a new combinatorial immunotherapy against nasopharyngeal carcinoma.
In this study, the EBV-targeting probe (L2) P4 reactivated latent EBV in EBV-positive nasopharyngeal cancer cells, increasing their BTN2A1 and BTN3A1 protein expression, thereby enhancing the Vδ 2 T cell-mediated cytotoxicity against the tumour cells in vitro and in a mice model. Further experiments found the underlying mechanism is due to (L2) P4 inducing the expression of EBV LMP1 protein, resulting in IFN-g/p-JNK and NLRC5 activation and subsequent expression of BTN2A1/BTN3A1 to ultimately enhancing the recognition of BTN2A1/BTN3A1-expressing by Vδ 2 T cells, thereby mediating killing. The identification of the LMP1-IFN-g/p-JNK-NLRC5-BTN2A1/BTN3A1 axis may lead to new insights and therapeutic targets for nasopharyngeal carcinoma and other EBV+ tumors together with Vδ 2 T cells.
The study was recently published in the biomedical journal "Theranostics" (2022 IF: 11.600). Dr Allen KL Cheung is the corresponding author while Ms Liu Yue ( Ph.D. student) in the research group, is the first author of the article.
(Source from HKBU Faculty of Sciences
