Rigorous research is ongoing and is anticipated to further impact our ability to improve outcomes in this population. Abstract Purpose of review: Transplant recipients are at risk for cytomegalovirus CMV infection and associated morbidity and mortality. Remarkably, patients with low levels lived almost twice as long as patients with high levels suggesting that HCMV infection of tumor cells alters the disease course in this patient group [ 3 ].
These results suggest either a systemic reactivation of HCMV within patients with glioblastoma which may be relevant for virus transport from periphery into the tumor tissues or shedding of viral DNA after reactivation of latent HCMV in tumor cells into the periphery. In fact, a pilot clinical study showed that the incidence of HCMV reactivation in patients receiving conventional chemotherapy without major immunosuppressive agents may be high without obvious HCMV disease [ 94 ].
It should also be noted that HCMV reactivation seems to be dependent on differentiation of myeloid lineage and inflammation [ 2,3 ]. In patients with different inflammatory disorders, HCMV reactivation was evident in inflamed tissues but not in non-inflamed tissue specimens from the same patient or healthy controls [ 3 ].
Therefore, inflammatory environment present in most solid tumors could contribute to local HCMV reactivation. Conversely, HCMV also exerts proinflammatory potential mainly owing to the production of numerous inflammatory mediators from infected cells [ 14 ].
Thus, HCMV reactivation in cancer tissues may enhance tumor inflammation and accelerate a malignant process. Many clinical and experimental findings suggest a contribution of HCMV to malignancy and chemoresistance of infected tumor cells from different entities. However, oncomodulation needs to be further defined in a systematic manner to increase the understanding of the phenomenon and to better translate the experimental results in more effective anticancer therapies.
First, standardization of highly sensitive techniques is necessary to detect low-grade HCMV infection of tumor tissues to reasonably compare pathologic studies from different groups. Moreover, the clinical relevance of experimentally defined oncomodulatory mechanisms induced by HCMV regulatory proteins and noncoding RNA needs to be examined. This includes the investigation of the HCMV oncomodulatory activity in the context of the internal cellular environment in tumor tissues and genetic and functional studies of HCMV strains isolated from patients' tumor samples.
Hereby, it is important to study HCMV-induced oncomodulation not only in infected tumor cells but also in stroma cells, because HCMV-induced changes in the tumor microenvironment may also contribute to oncomodulation.
Another central aim is to develop therapeutic strategies to suppress HCMV replication or to target viral regulatory proteins or noncoding RNA because persistent virus replication is supposed to be essential for oncomodulation. Clinical trials to evaluate the efficacy of antiviral treatment or HCMV-targeted immunotherapy in patients with malignant glioblastoma have just been started [ 3,94 ].
This finding supports that HCMV may be a potential immunotherapeutic target in HCMV-infected tumors and should therefore be a further impulse to strengthen our effor.
National Center for Biotechnology Information , U. Journal List Neoplasia v. Author information Article notes Copyright and License information Disclaimer. Address all correspondence to: Jindrich Cinatl, Jr. E-mail: ed. All rights reserved. This article has been cited by other articles in PMC. Abstract Although human cytomegalovirus HCMV is generally not regarded to be an oncogenic virus, HCMV infection has been implicated in malignant diseases from different cancer entities.
Introduction Human cytomegalovirus HCMV is a ubiquitous herpes virus that leads to a life-long persistence. Open in a separate window. Figure 1. Influence of HCMV on Cancer Cell Apoptosis Resistance to apoptosis is a common feature of cancer cells and represents a relevant chemoresistance mechanism [ 19,20,28—30 ]. Figure 2. Influence of HCMV on Cancer Cell Invasion, Migration, and Adhesion to the Endothelium Cancer cell invasion, migration, and adhesion to the endothelium play important roles during formation of metastases [ 52—54 ].
Influence of HCMV on Angiogenesis Recruitment of tumor vessels is an integral part of cancer initiation and progression [ 19,58,59 ]. Figure 3. Influence of HCMV on Chromosome Stability Human cytomegalovirus infection has been demonstrated to induce chromosome damage [ 82 ], and genetic instability is considered to be major driver of cancer progression [ 83,84 ].
Clinical Findings Although HCMV infection of tumor cells was initially reported 30 years ago in patients with carcinomas such as prostate or colon cancer, later pathologic investigations provided conflicting results [ 14 ]. Conclusions Many clinical and experimental findings suggest a contribution of HCMV to malignancy and chemoresistance of infected tumor cells from different entities. References 1. Molecular mechanisms of the modulatory effects of HCMV infection in tumor cell biology. Trends Mol Med.
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Prophylactic granulocyte transfusions during human bone marrow transplantation. Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell depleted stem cell transplantation. Community donors vs related donors for granulocyte transfusion therapy in hematopoietic transplantation: a comparative analysis of feasibility and outcome [abstract].
Therapeutic granulocyte transfusions: retrospective study of 34 patients [abstract]. Add comment Close comment form modal. Submit a comment. Comment title. You have entered an invalid code. Submit Cancel. Thank you for submitting a comment on this article. Your comment will be reviewed and published at the journal's discretion. Congenital cytomegalovirus infection can cause morbidity and even death.
After infection, CMV often remains latent, but it can reactivate at any time. Eventually, it causes mucoepidermoid carcinoma, and it may be responsible for prostate cancer.
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