Multi-omics reveals evolution from CD7-negative T cell dysregulation to EBV-positive LPD after CD7 CAR-T therapy.

Multi-omics profiling of post-CD7 CAR-T lymphoproliferative disorder (PCLD) shows CD7-negative T-cell dysregulation and a dominant Macro_IDO1 immunosuppressive niche linked to sustained EBV infection and transformation.

• Why it matters: EBV activation after CD7 CAR-T therapy is linked to EBV+ LPD, but the spatial tumor–immune mechanisms and cellular states driving this progression remain unclear.
• What they did: The study used single-nucleus RNA sequencing, ATAC sequencing, and Stereo-seq to spatially profile PCLD and compared it with classical PTLD, EBV-negative DLBCL, and normal lymph nodes.
• The result: In PCLD, CD7-negative T cells show limited proliferation and impaired antiviral activity against EBV, while Macro_IDO1 macrophages aggregate to form an immunosuppressive niche enriched for PD-1/PD-L1 interactions, enabling sustained EBV infection of B cells and malignant transformation.