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Multi-modal analysis reveals tumor and immune features distinguishing EBV-positive and EBV-negative post-transplant lymphoproliferative disorders.
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Multi-modal analysis reveals tumor and immune features distinguishing EBV-positive and EBV-negative post-transplant lymphoproliferative disorders. Cell reports. Medicine Toh, J., Reitsma, A. J., Tajima, T., Younes, S. F., Ezeiruaku, C., Jenkins, K. C., Peña, J. K., Zhao, S., Wang, X., Lee, E. Y., Glass, M. C., Kalesinskas, L., Ganesan, A., Liang, I., Pai, J. A., Harden, J. T., Vallania, F., Vizcarra, E. A., Bhagat, G., Craig, F. E., Swerdlow, S. H., Morscio, J., Dierickx, D., Tousseyn, T., Satpathy, A. T., Krams, S. M., Natkunam, Y., Khatri, P., Martinez, O. M. 2024: 101851Abstract
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.
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