Abstract
Background De novo tumors are a major cause of morbidity and mortality after long-term solid organ transplantation. Chronic immunosuppression strongly affects solid organ transplanted (SOT) patients’ immune system by promoting immune evasion strategies and reactivations of viruses with oncogenic potential, ultimately leading to cancer onset. In this scenario, an oncological Surveillance Protocol integrated with biobanking of peripheral blood samples and evaluation of immunovirological and molecular parameters was activated for SOT patients at CRO-IRCCS Aviano, with the aim of identifying suitable biomarkers of cancer development.MethodsAn exploratory longitudinal study was designed based on two serial peripheral blood samples collected at least three months apart. Forty nine SOT patients were selected and stratified by tumor onset during follow-up. Spontaneous T-cell responses to EBV, CMV and tumor associated antigens, EBV-DNA and CMV-DNA loads, and circulating TERT mRNA levels were investigated.ResultsSignificantly higher levels of circulating TERT mRNA were observed 3.5-23.5 months before and close to the diagnosis of cancer as compared to tumor-free patients. Plasmatic TERT mRNA levels >97.73 copies/mL at baseline were significantly associated with the risk of developing de novo tumors (HR=4.0, 95%C.I. = 1.4-11.5, p=0.01). In particular, the risk significantly increased by 4% with every ten-unit increment in TERT mRNA (HR=1.04, 95%C.I. = 1.01-1.07, p=0.01).ConclusionsAlthough obtained in an exploratory study, our data support the importance of identifying early biomarkers of tumor onset in SOT patients useful to modulate the pace of surveillance visits.
Highlights
Solid organ transplantation is currently recognized as the treatment of choice for patients with end-stage disease and the availability of potent anti-rejection drugs significantly reduced the occurrence of acute and chronic allograft rejections, even though long-term survival is still poor [1]
To address this relevant issue, we took advantage of the clinical and laboratory surveillance program for solid organ transplanted (SOT) patients recently activated at Centro di Riferimento Oncologico (CRO)-IRCCS Aviano
The routine clinical workup of these patients was implemented with the investigation of CD8 T-cell responses against Epstein Barr virus (EBV) and CMV antigens and “universal” tumor associated antigens (TAAs), the assessment of viral reactivations and quantification of circulating telomerase reverse transcriptase (TERT) mRNA in plasma as potential source of riskpredictive biomarkers for a broad spectrum of cancers, such as those occurring in SOT recipients
Summary
Solid organ transplantation is currently recognized as the treatment of choice for patients with end-stage disease and the availability of potent anti-rejection drugs significantly reduced the occurrence of acute and chronic allograft rejections, even though long-term survival is still poor [1]. Tumor development, viral infections/reactivations and cardiovascular complications are among the major causes of morbidity and mortality in solid organ transplanted (SOT) patients [2,3,4]. Chronic immunosuppression strongly affects solid organ transplanted (SOT) patients’ immune system by promoting immune evasion strategies and reactivations of viruses with oncogenic potential, leading to cancer onset. In this scenario, an oncological Surveillance Protocol integrated with biobanking of peripheral blood samples and evaluation of immunovirological and molecular parameters was activated for SOT patients at CRO-IRCCS Aviano, with the aim of identifying suitable biomarkers of cancer development
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