Pathogenesis of EBV tissue-positive PCNSL in the immunosuppressed, and potential implications for immunotherapy. (A) Mutations in the NF-κB and cell-cycling pathways and deletion of HLA class I/II molecules in EBV⁻ HIV⁻ PCNSL. (B) Viral transformation in EBV tissue-positive PCNSL, with the loss of host immunity providing no selection pressure to prevent presentation of EBV-immunogenic peptides by HLA I/II molecules. (C) EBV-specific viral specific T cells (VST) cross the blood–brain barrier to target the EBV⁺ malignant B cell.