Post-transplant lymphoproliferative disorders: from epidemiology to pathogenesis-driven treatment.
Post-transplant lymphoproliferative disorders (PTLDs) represent the most severe complication of both solid organ and hematopoietic stem cell transplantation. The Epstein-Barr Virus (EBV) is the main driver of PTLD, particularly those occurring early after transplantation. EBV-driven malignancies are associated with selective expression of latent viral proteins, but uncontrolled lytic replication may favor early phases of cell transformation. Besides immunodepression, persistent immune activation and chronic inflammation play an important role in both virus reactivation and expansion of EBV-infected B cells. EBV-induced immortalization requires the expression of telomerase. TERT, the rate-limiting component of the telomerase complex, is central in the switch from the lytic to the latent viral program, and TERT inhibition induces the EBV lytic cycle and cell death. Immunotherapy and combination of EBV lytic cycle inducers with antiviral drugs are promising strategies to improve the treatment of PTLD patients. This review is aimed at providing an update on the intriguing association between EBV and PTLD, mainly focusing on cases arising after kidney and liver transplantation, which account for the vast majority of transplants.
Epidemiology and Biostatistics Unit, Centro di Riferimento Oncologico (CRO)-IRCCS, National Cancer Institute, Aviano (PN), Italy; Section of Oncology and Immunology, Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy.
Maria Raffaella
MR
Petrara
Section of Oncology and Immunology, Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy.
Silvia
S
Giunco
Epidemiology and Biostatistics Unit, Centro di Riferimento Oncologico (CRO)-IRCCS, National Cancer Institute, Aviano (PN), Italy.
Diego
D
Serraino
Cancer Bio-Immunotherapy Unit, Centro di Riferimento Oncologico (CRO)-IRCCS, National Cancer Institute, Aviano (PN), Italy.
Riccardo
R
Dolcetti
Section of Oncology and Immunology, Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy; Viral Oncology Unit, Istituto Oncologico Veneto (IOV)-IRCCS, Padova, Italy. Electronic address: anita.derossi@unipd.it.
Anita
A
De Rossi
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D016377:Organ Transplantation / Q000009:adverse effects; D011183:Postoperative Complications / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D019098:Telomerase / Q000037:antagonists & inhibitors; D017735:Virus Latency
D000998:Antiviral Agents; D019098:Telomerase
EBV; Inflammation/immune activation; Latent/lytic viral cycle; PTLD; Telomerase; Treatment