Integrated multi-modal analysis reveals tumor and immune characteristics that distinguish Epstein-Barr virus-positive and -negative B cell post-transplant lymphoproliferative disorders [Affymetrix]

The highly prevalent oncogenic Epstein-Barr virus (EBV) can drive tumorigenesis with disrupted host immunity, causing malignancies including post-transplant lymphoproliferative disorders (PTLD). 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. Microarrays were used to elucidate the B cell intrinsic differences between B cells transformed with EBV and B cells transformed in the absence of EBV. Specifically, we profiled the transcriptome of five EBV(+) B cell lymphoma lines derived from patients with EBV(+) PTLD with morphology corresponding to diffuse large B cell lymphoma (DLBCL) (AB5, JB7, JC62, MF4, VB5), and two EBV(-) DLBCL cell lines (Pfeiffer, Toledo).