NGHIÊN CỨU TÁC ĐỘNG CỦA EBV LÊN MÔI TRƢỜNG VI THỂ KHỐI U VÀ ĐỘT BIẾN LIÊN QUAN TÍN HIỆU HOẠT HÓA NF-κB Ở LYMPHOMA HỆ THẦN KINH TRUNG ƢƠNG NGUYÊN PHÁT

Abstract

Objectives: 1) To determine the impact of EBV on TME and mutation pattern of NFkB in PCNSL. Methods: FFPE tissue samples of 39 PCNSL patients were collected from PA hospital and Canberra hospital. NanoString was used to measure gene expression of effectors (CD4, CD8, CD137 and CD56); checkpoints (PD-L1, PD-L2, TIM3 and LAG3) and Macrophage (CD68, CD163). Target Sequencing was performed to identify mutations in NF-kB pathway. Results: EBV+PCNSL exhibits immunosuppressive TME with the elevated level of all immune checkpoints (PD-L1, PD-L2, TIM3, LAG3) và M2 macrophage (CD163/CD68) compared with PCNSL (p < 0.05). This leads to the ineffective immune response in TME which contributes to the tumour growth in EBV+PCNSL. 80% PCNSL had mutations involved in NF-kB: MYD88 (64%), CD79A/B (56%), CARD11 (13%) and TBL1XR1 (33%) with the common co-occurrence of MYD88 and CD79B/A mutations. In contrast, only 22% of EBV+PCNSL had mutations in NF-kB (p<0.05) and these mutations are spares. Conclusion: EBV plays an important role in promoting the tumur growth via immunosuppressive TME, rather than via genetic alterations involved in NF-kB.