IFN-γ-induced CD4+ CADM1+ T cells emerged as malignancy-progressive biomarkers in EBV NK/T lymphoproliferative disorders and potential drivers of malignant expansion in AITL

作者：Jian Li, Yan Zhang, Qinhuan Luo, Daobin Zhou, Yiao Di, Wei Zhang, Chong Wei · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-3530 · 研究领域：Autoimmune and Inflammatory Disorders Research、Immune Cell Function and Interaction、Lymphoma Diagnosis and Treatment

Abstract Objective Epstein-Barr virus (EBV) infection of T and NK cells leads to EBV-associated NK/T-cell lymphoproliferative disorders (EBV NK/T LPDs), a spectrum of aggressive and poorly understood diseases that range from chronic inflammation to fulminant hemophagocytic lymphohistiocytosis. Accurate diagnosis remains challenging due to disease heterogeneity and technical barriers. Although immunostaining and PCR of biopsies are commonly used, obtaining biopsies is invasive and risky, and PCR of sorted cells often yields ambiguous results. Compared to EBV-associated B-cell neoplasms, which benefit from targeted therapies such as rituximab, EBV NK/T LPDs lack effective molecular therapies and respond poorly to chemotherapy. These diagnostic and therapeutic challenges are compounded by our limited understanding of pathogenesis and molecular mechanisms underlying the EBV NK/T LPDs. This study aims to characterize the immune and molecular landscape of EBV NK/T LPDs and to identify novel diagnostic biomarkers and therapeutic targets to improve patient outcomes. Methods We collected and analyzed single-cell RNA-sequencing (scRNA-seq) and TCR-sequencing (scTCR-seq) data of peripheral blood mononuclear cells (PBMCs) from 15 patients: 2 with infectious mononucleosis (IM), 8 with chronic active EBV (CAEBV) at various grades, 2 with EBV (+) angioimmunoblastic T-cell lymphoma (AITL), 2 with EBV (+) peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), and 1 with EBV (+) nodula...