Jiang X.-NYu B.-HYan W.-HLee JZhou X.-YLi X.-Q.LI-HSING LEE2022-11-112022-11-11202021624011https://www.scopus.com/inward/record.uri?eid=2-s2.0-85074610559&doi=10.1080%2f2162402X.2019.1683346&partnerID=40&md5=3d9505b11fa70cbe72f0527df309152dhttps://scholars.lib.ntu.edu.tw/handle/123456789/624843Background: B cells can function as antigen-presenting cells by presenting antigens captured by the B-cell receptor (BCR) on Class II Major Histocompatibility Complex (MHC II) to T cells. In addition, B-cells can also maintain immune homeostasis by expressing PD-L1 and suppressing T-cell activity. Epstein-Barr virus (EBV) infection can disrupt B-cell function and lead to B cell malignancies, including diffuse large B-cell lymphoma (DLBCL). Here we show that EBV-positive DLBCL (EBV+ DLBCL) has decreased expression of BCR and MHC II, but over-expressed PD-L1, which may lead to immune evasion. Methods: An EBV+ DLBCL cohort (n = 30) and an EBV- DLBCL control cohort (n = 83) were established. Immunostaining of PD-L1, MHC II, MHC II Transactivator (CIITA) and pBTK was performed on automated stainer. H-score was used to denote the results of staining of PD-L1 and pBTK. Break apart and deletion of CIITA locus was studied by fluorescent in situ hybridization. Surface immunoglobulin mean fluorescent insensitivity (MFI) was detected by flow cytometry to demonstrate the level BCR. Results: EBV+ DLBCL showed significantly lower expression of CIITA and MHC II compared to EBV- DLBCL. Genetic aberrations involving CIITA were also more common in EBV+ DLBCL, with 23% break apart events and 6% deletion events, comparted to 2% break apart and 0% deletion in EBV- DLBCL. In addition to the loss of antigen presentation molecule, the antigen capture receptor, BCR, was also down-regulated in EBV+ DLBCL. Accordingly, BCR signaling was also significantly decreased in EBV+ DLBCL as denoted by the respective pBTK levels. Conclusions: EBV+ DLBCL shows over expression of the T-cell inhibitory ligand, PD-L1. Antigen capture and presentation system were disrupted, and T-cell inhibitory molecule was hijacked in EBV+ DLBCL, which may contribute to immune escape in this high risk disease. Therapies targeting these aberrations may improve the outcome of patients with EBV+ DLBCL. © 2019, © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.B-cell receptor; diffuse large B-cell lymphoma; EBV; immune escape; MHC II; PD-L1B lymphocyte receptor; lymphocyte membrane immunoglobulin; major histocompatibility antigen class 2; programmed death 1 ligand 1; adult; aged; antigen presentation; antigen presenting cell; Article; B lymphocyte; cell disruption; clinical article; cohort analysis; controlled study; diffuse large B cell lymphoma; down regulation; Epstein Barr virus infection; female; flow cytometry; fluorescence in situ hybridization; gene deletion; gene overexpression; human; human cell; immune evasion; immune response; immunofluorescence microscopy; immunohistochemistry; immunophenotyping; immunosuppressive treatment; male; protein expression; retrospective study; T cell depletion; transcription initiation; very elderly; antigen presentation; complication; Epstein Barr virus; genetics; T lymphocyte; Antigen Presentation; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; In Situ Hybridization, Fluorescence; Lymphoma, Large B-Cell, Diffuse; T-Lymphocytesjournal article10.1080/2162402X.2019.1683346320022942-s2.0-85074610559