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The presence of EBV infected B cells in postmortem multiple sclerosis (MS) brain tissue suggests immune evasion strategies. Using immunohistochemical techniques we analysed the expression of the immune checkpoint molecule PD-L1 and its receptor PD-1 in MS brains containing B cell-enriched perivascular infiltrates and meningeal follicles, a major EBV reservoir. PD-1 and PD-L1 immunoreactivities were restricted to CNS-infiltrating immune cells. PD-L1 was expressed on B cells, including EBV infected B cells, while PD-1 was expressed on many CD8+ T cells, including EBV-specific CD8+ T-cells, and fewer CD4+ T cells. PD-L1+ cells and EBV infected cells were in close contact with PD-1+ T cells. PD-L1 expressed by EBV infected B cells could favour local immune evasion leading to EBV persistence and immunopathology in the MS brain. [Display omitted] • Most EBV infected B cells in the MS brain express the immune checkpoint molecule PD-L1. • The PD-L1 receptor PD-1 is expressed on MS brain-infiltrating T cells. • CNS-infiltrating EBV-specific CD8 T cells also express PD-1. • PD-1+ T cells contact PD-L1+ and EBV infected cells in MS lesions and meninges. • The PD-1-PD-L1 pathway may limit EBV elimination and sustain inflammation in the MS brain. [ABSTRACT FROM AUTHOR]

Recent studies have revealed that tumor immunotherapy resistance is influenced by ADAR-mediated RNA editing, but its targets remain unelucidated. Our current study identified the poliovirus receptor (PVR) oncogene, which encodes an immune checkpoint in colorectal cancer (CRC), as a potential target for RNA editing. We performed transcriptome sequencing analysis and experimental validation in two Chinese CRC cohorts. PVR and ADAR expressions significantly increased in CRC tumors and showed positive correlations in both cohorts, coupled with upregulated PVR RNA editing in CRC tumors. Manipulation of ADAR expression by over-expression or knockdown substantially changed PVR expression and RNA editing in HTC116 CRC cells. Luciferase reporter and actinomycin D assays further revealed that RNA editing in PVR 3′-UTR could upregulate PVR RNA expression, probably by increasing the RNA stability. By increasing PVR expression, ADAR-mediate RNA editing might contribute to tumor- and immune-related gene functions and pathways in CRC. Moreover, a signature combining PVR RNA editing and expression showed promising predictive performance in CRC diagnosis in both Chinese CRC cohorts. Our findings thus highlight the importance of ADAR-mediated RNA editing in PVR up-regulation in CRC tumors and provide new insight into the application of PVR RNA editing as a novel diagnostic biomarker for CRC. • Immune checkpoint PVR was identified as a novel target of ADAR-mediated RNA editing in two Chinese CRC cohorts. • Elevated ADAR expression significantly upregulated PVR RNA editing and expression in CRC. • RNA editing in the PVR 3′-UTR significantly increased the RNA expression, probably by increasing RNA stability. • A signature combining PVR RNA editing and expression showed promising performance in CRC diagnosis in both Chinese cohorts. [ABSTRACT FROM AUTHOR]