Toh Jiaying, Reitsma Andrea J, Tajima Tetsuya, Younes Sheren F, Ezeiruaku Chimere, Jenkins Kayla C, Peña Josselyn K, Zhao Shuchun, Wang Xi, Lee Esmond Y Z, Glass Marla C, Kalesinskas Laurynas, Ganesan Ananthakrishnan, Liang Irene, Pai Joy A, Harden James T, Vallania Francesco, Vizcarra Edward A, Bhagat Govind, Craig Fiona E, Swerdlow Steven H, Morscio Julie, Dierickx Daan, Tousseyn Thomas, Satpathy Ansuman T, Krams Sheri M, Natkunam Yasodha, Khatri Purvesh, Martinez Olivia M
Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA, USA; PhD Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA.
Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA, USA.
Cell Rep Med. 2024 Dec 17;5(12):101851. doi: 10.1016/j.xcrm.2024.101851. Epub 2024 Dec 9.
The oncogenic Epstein-Barr virus (EBV) can drive tumorigenesis with disrupted host immunity, causing malignancies including post-transplant lymphoproliferative disorders (PTLDs). PTLD can also arise in the absence of EBV, but the biological differences underlying EBV(+) and EBV(-) B cell PTLD and the associated host-EBV-tumor interactions remain poorly understood. Here, we reveal the core differences between EBV(+) and EBV(-) PTLD, characterized by increased expression of genes related to immune processes or DNA interactions, respectively, and the augmented ability of EBV(+) PTLD B cells to modulate the tumor microenvironment through elaboration of monocyte-attracting cytokines/chemokines. We create a reference resource of proteins distinguishing EBV(+) B lymphoma cells from EBV(-) B lymphoma including the immunomodulatory molecules CD300a and CD24, respectively. Moreover, we show that CD300a is essential for maximal survival of EBV(+) PTLD B lymphoma cells. Our comprehensive multi-modal analyses uncover the biological underpinnings of PTLD and offer opportunities for precision therapies.
致癌性爱泼斯坦-巴尔病毒（EBV）可通过破坏宿主免疫驱动肿瘤发生，引发包括移植后淋巴增殖性疾病（PTLD）在内的恶性肿瘤。PTLD也可在无EBV的情况下发生，但EBV阳性和EBV阴性B细胞PTLD的生物学差异以及相关的宿主-EBV-肿瘤相互作用仍知之甚少。在此，我们揭示了EBV阳性和EBV阴性PTLD之间的核心差异，其特征分别为与免疫过程或DNA相互作用相关基因的表达增加，以及EBV阳性PTLD B细胞通过分泌吸引单核细胞的细胞因子/趋化因子来调节肿瘤微环境的能力增强。我们创建了一个区分EBV阳性B淋巴瘤细胞和EBV阴性B淋巴瘤的蛋白质参考资源，分别包括免疫调节分子CD300a和CD24。此外，我们表明CD300a对于EBV阳性PTLD B淋巴瘤细胞的最大存活至关重要。我们全面的多模态分析揭示了PTLD的生物学基础，并为精准治疗提供了机会。
