About this Research Topic
The Epstein-Barr virus (EBV), the first human cancer virus, is a double-stranded DNA gamma-1 herpesvirus that infects more than 90% of the adult population worldwide. EBV was discovered through its association with Burkitt lymphoma over fifty years ago and was the first human virus whose genome was fully sequenced. Following primary infection, the virus finds its permanent reservoir in resting memory B cells, although other cell types can also be infected. EBV-associated cancers are an infrequent outcome of EBV’s latent infection but, in light of the high global prevalence of the infection, they represent a very significant fraction of the cancer burden worldwide. Globally, EBV is estimated to be responsible for ~200,000 new cancer cases each year, including lymphomas (Burkitt’s lymphoma, Hodgkin’s lymphoma, NK/T-cell lymphoma, and immunosuppression-related lymphomas), epithelial cancers (nasopharyngeal carcinoma, ~10% of gastric carcinomas), and a very diverse spectrum or rare lymphoproliferative diseases.
The essential feature of EBV-associated cancer is the presence of EBV-infected tumor cells in the diagnostic biopsy, although a co-factor role for EBV has also been proposed in malignancies where the virus is found primarily in the tumor microenvironment. In addition, cell-free, plasma EBV DNA (pEBVd) levels usually correlate with the presence of EBV in tumor tissue in EBV-associated cancers, and may be a better biomarker to define these malignancies. The mechanisms leading to cell transformation in EBV-infected cells have been studied for many decades, but new discoveries continue to be generated, in particular in regard to the protean ways by which EBV hijacks the cellular genetic and epigenetic machinery to maintains its latent state in the host, and occasionally replicate and infect new cells. Much progress has recently been made in characterizing the pattern of EBV gene expression and EBV-induced epigenetic aberrations in tumor cells and their precursors. EBV-specific immune responses are critical to maintain latency, and immune suppression often leads to the outgrowth of EBV-infected clones and lymphoma. Complex interactions in the tumor microenvironment are also important for the development of EBV-associated cancers.
Importantly, EBV also represents a potential target for novel cancer diagnostic and therapeutic approaches, including the possibility of prevention by vaccination. This Research Topic will highlight current knowledge of EBV-associated cancers, spanning basic biology and virology, global prevalence landscape, risk factors, immune response, novel therapies, and potential vaccine strategies.
The essential feature of EBV-associated cancer is the presence of EBV-infected tumor cells in the diagnostic biopsy, although a co-factor role for EBV has also been proposed in malignancies where the virus is found primarily in the tumor microenvironment. In addition, cell-free, plasma EBV DNA (pEBVd) levels usually correlate with the presence of EBV in tumor tissue in EBV-associated cancers, and may be a better biomarker to define these malignancies. The mechanisms leading to cell transformation in EBV-infected cells have been studied for many decades, but new discoveries continue to be generated, in particular in regard to the protean ways by which EBV hijacks the cellular genetic and epigenetic machinery to maintains its latent state in the host, and occasionally replicate and infect new cells. Much progress has recently been made in characterizing the pattern of EBV gene expression and EBV-induced epigenetic aberrations in tumor cells and their precursors. EBV-specific immune responses are critical to maintain latency, and immune suppression often leads to the outgrowth of EBV-infected clones and lymphoma. Complex interactions in the tumor microenvironment are also important for the development of EBV-associated cancers.
Importantly, EBV also represents a potential target for novel cancer diagnostic and therapeutic approaches, including the possibility of prevention by vaccination. This Research Topic will highlight current knowledge of EBV-associated cancers, spanning basic biology and virology, global prevalence landscape, risk factors, immune response, novel therapies, and potential vaccine strategies.
Keywords: EBV, Lymphoma, lymphoproliferative, microenvironment, epigenetic
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