Human cytomegalovirus seropositivity is associated with decreased survival in glioblastoma patients

Foster, Haidn; Piper, Keenan; DePledge, Lisa; Li, Hsin-Fang; Scanlan, James M.; Jae-Guen, Yoon; Boeckh, Michael; Cobbs, Charles S.

doi:10.1093/noajnl/vdz020

Cited by 19 publications

(16 citation statements)

References 32 publications

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“…Our results concerning glioblastoma patients fit clinical reports proposing that glioblastoma exhibits characteristics of both cancer and neurologic diseases (42), and recently, it has been shown that HCMV seropositivity is associated with decreased survival in patients with glioblastoma (43).…”

Section: Hcmv-associated Encephalopathysupporting

confidence: 90%

Early Mortality of Brain Cancer Patients and its Connection to Cytomegalovirus Reactivation During Radiochemotherapy

Goerig

Frey

Korn

et al. 2020

Clinical Cancer Research

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If routine diagnostics are inconclusive, neurologic deterioration and death of patients with brain cancer are attributed to tumor or therapy. Therefore, diagnosing symptoms of encephalopathy caused by human cytomegalovirus (HCMV) reactivation remains uncommon. We investigated the role of HCMV reactivation in neurologic decline and clinical outcome after the start of radiochemotherapy.Experimental Design: HCMV analyses and extended MRI studies including additional independent retrospective neuroradiologic evaluation were performed at predetermined intervals and in case of sudden neurologic decline for 118 adult patients: 63 histologically proven high-grade gliomas, 55 with brain metastases. Immunophenotyping from simultaneously taken whole-blood samples was carried out to detect immune cells serving as prognostic marker for HCMV-associated complications. Symptomatic viremia and overall survival (OS) were the endpoints.Results: Twenty-four percent (28/118) of all patients (12/44 glioblastoma, 3/13 anaplastic astrocytoma; 8/31 non-small cell lung cancer (NSCLC), 13/24 other brain metastases) developed HCMVviremia during or within 4 weeks after radiotherapy; 21 of 28 patients experienced concurrent major neurologic decline, reversible by antiviral treatment. Identified by immunophenotyping, pretherapeutically low basophil counts predicted a high-risk for HCMV-associated encephalopathy (glioblastoma: P ¼ 0.002, NSCLC: P ¼ 0.02). Median OS was substantially reduced after HCMV-associated encephalopathy without MRI signs of tumor progression [glioblastoma: 99 vs. 570 days (calculated 1-year OS: 22% vs. 69%; P ¼ 0.01) and NSCLC: 47 vs. 219 days (calculated 1-year OS: 0% vs. 32%; P ¼ 0.02)].Conclusions: For patients with brain cancer, HCMV reactivation after the start of radiochemotherapy is a frequent risk for cognitively detrimental but treatable encephalopathy and premature death. Routinely performed HCMV diagnostics, assessing basophil counts and study-based anti-viral regimens, are necessary to combat this hidden threat.See related commentary by Lawler et al., p. 3077

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Section: Hcmv-associated Encephalopathysupporting

confidence: 90%

Early Mortality of Brain Cancer Patients and its Connection to Cytomegalovirus Reactivation During Radiochemotherapy

Goerig

Frey

Korn

et al. 2020

Clinical Cancer Research

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“…In the context of brain neoplasia, human CMV increases glioblastoma neurosphere proliferation and p-STAT3 levels, these findings suggested the existence of an association between CMV infection and STAT3-dependend modulation in glioma formation/ progression, together with tumor suppressor mutations (51). Consistent with these findings, CMV seropositivity correlates with worse prognosis in GBM patients (52). This discovery provides the basis of viral antigen targeting immune therapies in GBM.…”

Section: Non-engineered Immune Cell Approachessupporting

confidence: 61%

Innovative and Promising Strategies to Enhance Effectiveness of Immunotherapy for CNS Tumors: Where Are We?

et al. 2021

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Although there are several immunotherapy approaches for the treatment of Central Nervous System (CNS) tumors under evaluation, currently none of these approaches have received approval from the regulatory agencies. CNS tumors, especially glioblastomas, are tumors characterized by highly immunosuppressive tumor microenvironment, limiting the possibility of effectively eliciting an immune response. Moreover, the peculiar anatomic location of these tumors poses relevant challenges in terms of safety, since uncontrolled hyper inflammation could lead to cerebral edema and cranial hypertension. The most promising strategies of immunotherapy in neuro-oncology consist of the use of autologous T cells redirected against tumor cells through chimeric antigen receptor (CAR) constructs or genetically modified T-cell receptors. Trials based on native or genetically engineered oncolytic viruses and on vaccination with tumor-associated antigen peptides are also under evaluation. Despite some sporadic complete remissions achieved in clinical trials, the outcome of patients with CNS tumors treated with different immunotherapeutic approaches remains poor. Based on the lessons learned from these unsatisfactory experiences, novel immune-therapy approaches aimed at overcoming the profound immunosuppressive microenvironment of these diseases are bringing new hope to reach the cure for CNS tumors.

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“…The herpesvirus's Epstein-Barr virus, herpes-simplex 1/2, has been extensively evaluated in human cancers; yet, the evidence in central nervous system tumors is contradictory [43,44]. Cytomegalovirus (CMV) was associated with glioma where serologic investigations into risk/survival and the presence of CMV within tumors have again provided inconsistent evidence of a causal link between CMV and glioma development [45][46][47][48]. However, recently two anti-CMV therapeutics have provided evidence of increased patient survival after receiving valganciclovir or a pp65 based treatment [49,50].…”

Section: Immune Related Factors: Viruses Allergy and Hlamentioning

confidence: 99%

Epidemiology of Brain and Other CNS Tumors

Ostrom

Francis

Barnholtz‐Sloan

2021

Curr Neurol Neurosci Rep

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Purpose of Review Brain and other central nervous system (CNS) tumors, while rare, cause significant morbidity and mortality across all ages. This article summarizes the current state of the knowledge on the epidemiology of brain and other CNS tumors. Recent Findings For childhood and adolescent brain and other CNS tumors, high birth weight, non-chromosomal structural birth defects and higher socioeconomic position were shown to be risk factors. For adults, increased leukocyte telomere length, proportion of European ancestry, higher socioeconomic position, and HLA haplotypes increase risk of malignant brain tumors, while immune factors decrease risk. Summary Although no risk factor accounting for a large proportion of brain and other CNS tumors has been discovered, the use of high throughput “omics” approaches and improved detection/measurement of environmental exposures will help us refine our current understanding of these factors and discover novel risk factors for this disease.

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Human cytomegalovirus seropositivity is associated with decreased survival in glioblastoma patients

Cited by 19 publications

References 32 publications

Early Mortality of Brain Cancer Patients and its Connection to Cytomegalovirus Reactivation During Radiochemotherapy

Early Mortality of Brain Cancer Patients and its Connection to Cytomegalovirus Reactivation During Radiochemotherapy

Innovative and Promising Strategies to Enhance Effectiveness of Immunotherapy for CNS Tumors: Where Are We?

Epidemiology of Brain and Other CNS Tumors

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