The interplay between Epstein-Barr virus and the immune system: a rationale for adoptive cell therapy of EBV-related disorders

Abstract

The Epstein-Barr virus has evolved a plethora of strategies to evade immune system recognition and to establish latent infection in memory B cells, where the virus resides lifelong without any consequence in the majority of individuals. However, some imbalances in the equilibrium between the inherent virus transforming properties and the host immune system can lead to the development of different tumors, such as lymphoproliferative disorders, Hodgkin's lymphoma, Burkitt's lymphoma, and nasopharyngeal carcinoma. The expression of viral antigens in malignant cells makes them suitable targets for immunotherapeutic approaches, which are mainly based on the ex vivo expansion of EBV-specific T cells. Indeed, the infusion of virus-specific cytotoxic T lymphocytes has proved not only to be safe and effective, but also capable of restoring or inducing a protective anti-virus immunity, which is lacking, albeit to a different extent, in every EBV-driven malignancy. The purpose of this review is to summarize the results of adoptive immunotherapy approaches for EBV-related malignancies, with particular emphasis on the immunological and virological aspects linked to the clinical responses obtained. Data collected confirm the clinical relevance of the use of EBV-specific cytotoxic T lymphocytes in the field of adoptive immunotherapy and suggest the increasing importance of this approach also against other tumors, concurrent with the increasing knowledge of the intimate and continuous interplay between the virus and the host immune system. -related disorders. Haematologica 210;95(10):1769-1777. doi:10.3324/haematol.2010 Citation: Merlo A, Turrini R, Dolcetti R, Martorelli D, Muraro E, Comoli P, and Rosato A. The interplay between Epstein-Barr virus and the immune system: a rationale for adoptive cell therapy of EBV ©2010 Ferrata Storti Foundation. This is an open-access paper.The interplay between Epstein-Barr virus and the immune system: a rationale for adoptive cell therapy of EBV-related disorders

Integrated Analysis of Multiple Gene Expression Profiling Datasets Revealed Novel Gene Signatures and Molecular Markers in Nasopharyngeal Carcinoma

“…These dysregulated genes suggested that the immune response was silenced in NPC. In addition, NPC is closely associated with persistent Epstein-Barr virus (EBV) infection, which has evolved a plethora of strategies to evade immune system recognition and to establish latent infection in memory B cells (28). Seven downregulated genes, CR2, C3, CLU, CD55, FOXJ1, C4A, and BCL6 were enriched in the B-cell-mediated immunity response.…”

How I treat posttransplant lymphoproliferative disorders

“…[78][79][80] Impressive results with very favorable toxicity profiles have also been obtained by prophylactic and preemptive administration of EBVspecific cytotoxic T lymphocytes (CTLs). 81 Despite these results, wide applicability of this approach has been limited due to high costs, the labor-intensive procedure, and availability difficulties. However, new strategies to develop more rapid approaches for generating virusspecific T cells and the introduction of a third-party bank with HLA-typed EBV-specific CTLs might alter the therapeutic landscape of PTLD in the near future.…”

Posttransplant Lymphoproliferative Disorders Following Kidney Transplantation

“…105,106 Due to this strong alloreactive mediated complications, further attempts were made to isolate expanded EBV-specific CTLs. By infusing these CTLs, both autologous (recipient derived PTLD) and allogeneic (isolated from the donor itself or from a bank of partial HLA-matched voluntary donors), promising results were obtained in PTLD patients after SOT, recently reviewed by Merlo et al 107 However, wide applicability has been limited so far because of pronounced labor-intensive procedure and by availability problems.…”