Journal
BIOMOLECULES
Volume 12, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/biom12030397
Keywords
Epstein-Barr virus; immune checkpoints; Hodgkin lymphoma; non-Hodgkin lymphomas; gastric adenocarcinomas; EBV-associated; viral oncoproteins; viral ncRNAs; immunotherapy; immune checkpoint blockade; cancer management
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Funding
- Sao Paulo Research Foundation (FAPESP) [2019/14324-9]
- Coordination for the Improvement of Higher Education (CAPES)
- Brazilian National Council for Scientific and Technological Development (CNPq)
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The Epstein-Barr Virus (EBV) is involved in the development of various human cancers and may interfere with immune checkpoint molecules. This has implications for the clinical management of EBV-associated malignancies.
The Epstein-Barr Virus (EBV) is a gammaherpesvirus involved in the etiopathogenesis of a variety of human cancers, mostly of lymphoid and epithelial origin. The EBV infection participates in both cell transformation and tumor progression, also playing an important role in subverting immune responses against cancers. The homeostasis of the immune system is tightly regulated by inhibitory mechanisms affecting key immune effectors, such as T lymphocytes and NK cells. Collectively known as immune checkpoints, these mechanisms rely on a set of cellular receptors and ligands. These molecules may be candidate targets for immune checkpoints blockade-an emergent and promising modality of immunotherapy already proven to be valuable for a variety of human cancers. The EBV was lately suspected to interfere with the expression of immune checkpoint molecules, notably PD-1 and its ligands, found to be overexpressed in cases of Hodgkin lymphoma, nasopharyngeal, and gastric adenocarcinomas associated with the viral infection. Even though there is compelling evidence showing that the EBV interferes with other immune checkpoint regulators (e.g., CTLA-4, LAG-3, TIM-3, and VISTA), the published data are still scarce. Herein, we discuss the current state of the knowledge on how the EBV interferes with the activity of immune checkpoints regulators, as well as its implications considering the immune checkpoints blockade for clinical management of the EBV-associated malignancies, notably lymphomas.
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