Medical Research: What is the background for this study?
Dr. Ferlini: Our aim is to understand why some cancer patients respond well to conventional treatment while others suffer progressive disease. Nextgen sequencing technologies provide data that shed light on the mechanisms underlying differences in clinical outcome. However, analyses utilizing these data have been focused on human genes. This is to be expected given that the subjects under investigation are indeed humans. We adopted a novel approach in this and a prior study which involved in-depth, comprehensive mapping of microRNA sequences in human cancers to viral genes to assess their presence and significance.
Medical Research: What are the main findings?
Dr. Ferlini: We discovered a surprising number of viral microRNA sequences in a wide variety of cancer tissues. We also documented an interplay between these viral microRNAs and genes related to anticancer immunity. Both viruses and cancers share a common goal of suppressing the immune system to promote their own survival. Synergistic immunosuppression seems particularly relevant for the Epstein Barr virus, an unfortunate fact given its ubiquity in human populations. After the acute phase of EBV infection, the virus persists indefinitely in a dormant state inside B lymphocytes. When cancers grow, they create a protected microenvironment in which anticancer immunity is suppressed. We have obtained evidence suggesting that when EBV infected B cells circulate within these domains, the virus becomes reactivated and produces microRNAs which further amplify immunosuppressive genes.
Medical Research: What should clinicians and patients take away from your report?
Dr. Ferlini: EBV has been implicated for decades as an oncogenic virus in malignancies, particularly lymphomas and nasopharyngeal carcinomas. Our study characterizes the role of the EBV reactivation as a determinant of cancer aggressiveness across a broad spectrum of cancer types. This information can potentially be harnessed to identify subpopulations of patients at particular risk for treatment failure. For early stage patients, this may be of particular importance. It may point the way toward novel therapeutic options that specifically reverse immunosuppression as a supplement to standard treatment protocols.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Ferlini: Our analyses were performed on nucleic acid sequences present in cancer tissues. Ideally, blood would be the preferred sample due to its accessibility at all stages of illness. Future efforts should assess viral, particularly EBV, reactivation in blood from cancer patients. We are optimistic that circulating viral microRNAs in blood will fulfill their promise as biomarkers of cancer-related immunosuppression.
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Dr. Cristiano Ferlini, MD (2015). Epstein Barr Virus and Cancers Suppress Immune System To Promote Their Own Survival