Epstein-Barr virus (EBV) is one of the most prevalent viruses in humans, infecting about 95% of global population by adult age. The past five decades of research has established EBV as a tumor virus implicated in variable fractions of several types of cancer, including Burkitt lymphoma, post-transplant lymphoproliferative disease, acquired immunodeficiency syndrome-associated B-cell lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. Although approximately 200,000 cases of EBV-associated malignancies are diagnosed each year, these represent only a small minority of EBV-infected people at the global scale. The key to such a low penetrance of EBV-driven cancers is that the virus primarily infects immune system’s B cells, and EBV-induced transformation turns B cells into potent antigen-presenting cells (APC), eliciting superiorly strong T cell-mediated immune surveillance. Although it has been long-held that T cells just target various EBV antigens, recent findings from human in vitro studies and mouse models suggest that the elicited T cells can also target a wide range of EBV-induced cellular antigens known to function as tumor-associated antigens (TAA). Given that TAAs are often shared by multiple tumors, this means that EBV infection can induce broad anti-tumor immunity.
Further efforts are needed to identify cellular antigens, such as TAAs, expressed by EBV-infected/-transformed B cells and characterize their elicited T cell responses in EBV-infected individuals. In this regard, several findings in recent literature are particularly encouraging. These include observations that in individuals at early stages of infection, activated “bystander” T cells (of unknown specificities) dominate over EBV-specific T cells; that T cell responses to several known TAAs can be detected in patients receiving T cells stimulated by EBV-transformed B cells to treat EBV-associated lymphomas; and that in a xenograft model of EBV-unrelated tumor, some tumor-infiltrating T cells can clonally expand in response to EBV-transformed B cells and appear to target certain shared TAAs. These findings also urge studies to unveil the likely protective effect, and therapeutic potential, of TAA-specific T cells in EBV-related malignancies, as well as in EBV-unrelated cancers through targeting shared TAAs. For comparison, parallel studies of EBV-specific T cells in EBV-related malignancies will also be valuable.
To advance the understanding of EBV-induced T cell immunity in cancers, in this collection we welcome submission of original research, case reports, reviews, and perspective articles addressing the following aspects:
• Identifying cellular antigens, such as TAAs, expressed by EBV-infected/-transformed B cells and demonstrating their recognition by T cells in EBV-infected individuals.
• Kinetics of EBV-induced TAA-specific T cells in vivo, in comparison with EBV-specific T cells.
• Contributions of TAA-specific and EBV-specific T cells in therapy against EBV-associated cancers.
• Role of EBV-induced TAA-specific T cells in immune surveillance or therapy (such as checkpoint blockade therapy) of EBV-unrelated cancers, in humans or animal models.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Topic Editor Boachun Zhang has a patent pertaining to use of the EBV molecule LMP1 for cancer immunotherapy, but this does not concern research that will be covered by this special issue. Topic Editor Chrisitan Münz has contract grants from Roche and Novartis, but they do not concern research that will be covered by this special issue. Topic Editor Josef Mautner declares no competing interests with regard to the Research Topic subject
Epstein-Barr virus (EBV) is one of the most prevalent viruses in humans, infecting about 95% of global population by adult age. The past five decades of research has established EBV as a tumor virus implicated in variable fractions of several types of cancer, including Burkitt lymphoma, post-transplant lymphoproliferative disease, acquired immunodeficiency syndrome-associated B-cell lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. Although approximately 200,000 cases of EBV-associated malignancies are diagnosed each year, these represent only a small minority of EBV-infected people at the global scale. The key to such a low penetrance of EBV-driven cancers is that the virus primarily infects immune system’s B cells, and EBV-induced transformation turns B cells into potent antigen-presenting cells (APC), eliciting superiorly strong T cell-mediated immune surveillance. Although it has been long-held that T cells just target various EBV antigens, recent findings from human in vitro studies and mouse models suggest that the elicited T cells can also target a wide range of EBV-induced cellular antigens known to function as tumor-associated antigens (TAA). Given that TAAs are often shared by multiple tumors, this means that EBV infection can induce broad anti-tumor immunity.
Further efforts are needed to identify cellular antigens, such as TAAs, expressed by EBV-infected/-transformed B cells and characterize their elicited T cell responses in EBV-infected individuals. In this regard, several findings in recent literature are particularly encouraging. These include observations that in individuals at early stages of infection, activated “bystander” T cells (of unknown specificities) dominate over EBV-specific T cells; that T cell responses to several known TAAs can be detected in patients receiving T cells stimulated by EBV-transformed B cells to treat EBV-associated lymphomas; and that in a xenograft model of EBV-unrelated tumor, some tumor-infiltrating T cells can clonally expand in response to EBV-transformed B cells and appear to target certain shared TAAs. These findings also urge studies to unveil the likely protective effect, and therapeutic potential, of TAA-specific T cells in EBV-related malignancies, as well as in EBV-unrelated cancers through targeting shared TAAs. For comparison, parallel studies of EBV-specific T cells in EBV-related malignancies will also be valuable.
To advance the understanding of EBV-induced T cell immunity in cancers, in this collection we welcome submission of original research, case reports, reviews, and perspective articles addressing the following aspects:
• Identifying cellular antigens, such as TAAs, expressed by EBV-infected/-transformed B cells and demonstrating their recognition by T cells in EBV-infected individuals.
• Kinetics of EBV-induced TAA-specific T cells in vivo, in comparison with EBV-specific T cells.
• Contributions of TAA-specific and EBV-specific T cells in therapy against EBV-associated cancers.
• Role of EBV-induced TAA-specific T cells in immune surveillance or therapy (such as checkpoint blockade therapy) of EBV-unrelated cancers, in humans or animal models.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Topic Editor Boachun Zhang has a patent pertaining to use of the EBV molecule LMP1 for cancer immunotherapy, but this does not concern research that will be covered by this special issue. Topic Editor Chrisitan Münz has contract grants from Roche and Novartis, but they do not concern research that will be covered by this special issue. Topic Editor Josef Mautner declares no competing interests with regard to the Research Topic subject
