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HKBU research sheds lights on immunotherapy against nasopharyngeal cancer

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The treatment of nasopharyngeal carcinoma has been based on mainly radiotherapy, chemotherapy, and surgery, but such treatments have significant side effects, limited effectiveness, and a high recurrence rate. Recently, a research team led by Dr. Allen KL Cheung, Department of Biology, Hong Kong Baptist University revealed that EBV membrane protein LMP1 plays a vital role in mediating the killing of nasopharyngeal cancer cells by adoptively transferred Vd2  T cells, which shed light on a new combinatorial immunotherapy against nasopharyngeal carcinoma.
 

The study showed that 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 Vd2 T cell-mediated cytotoxicity against the tumour cells in vitro and in a mice model.

 

This study demonstrated the effectiveness of using the EBV-targeting probe (L2)P4 and adoptive γδ T cells as a promising combinatorial immunotherapy against nasopharyngeal cancer; and the research findings may lead to new insights and therapeutic targets for nasopharyngeal carcinoma and other EBV+ tumors together with Vd2 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.

 

HKBU’s further experiments found the underlying mechanism is due to (L2) P4 inducing the expression of EBV LMP1 protein, resulting in IFN-/p-JNK and NLRC5 activation and subsequent expression of BTN2A1/BTN3A1 to ultimately enhancing the recognition of BTN2A1/BTN3A1-expressing by V2 T cells, thereby mediating killing.

HKBU’s further experiments found the underlying mechanism is due to (L2) P4 inducing the expression of EBV LMP1 protein, resulting in IFN-/p-JNK and NLRC5 activation and subsequent expression of BTN2A1/BTN3A1 to ultimately enhancing the recognition of BTN2A1/BTN3A1-expressing by V2 T cells, thereby mediating killing.

 

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Dr Allen KL Cheung

Dr Allen KL Cheung

DEPARTMENT OF BIOLOGY

Reference

  • Liu Y, Lui KS, Ye Z, Fung TY, Chen L, Sit PY, Leung CY, Mak NK, Wong KL, Lung HL, Tanaka Y, Cheung AKL. EBV latent membrane protein 1 augments γδ T cell cytotoxicity against nasopharyngeal carcinoma by induction of butyrophilin molecules. Theranostics 2023; 13(2):458-471. doi:10.7150/thno.78395.https://www.thno.org/v13p0458.htm