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Epstein-Barr virus-associated tumors: which T-cells are crucial for tumor control?

Some T-cell subsets can inhibit the growth of tumors that are associated with the Epstein-Barr virus, while others promote such growth. Inhibition is mediated by T-cells recognizing viral or cellular components of the tumor. These are the findings of a team of scientists from the Helmholtz Zentrum München (HMGU) and the Technische Universität München (TUM) that have just been published in the 'PLOS Pathogens' journal. These findings may lead to the development of more effective immunotherapies and vaccines.

Prof. Dr. Uta Behrends, PD Dr. Josef Mautner; Source: HMGU

More than 90% of the world’s population is infected with the Epstein-Barr virus (EBV). While primary infection with EBV in early childhood is often asymptomatic, delayed primary infection later in life may cause the syndrome of infectious mononucleosis. In addition, EBV is associated with several human malignancies, e.g. Burkitt’s lymphoma or lymphoproliferative disorders in immunocompromised patients.

T-immune cells* are crucial for the control of EBV infection. In their study, the team headed by Dr. Stefanie Linnerbauer, PD Dr. Josef Mautner and Prof. Dr. Uta Behrends from the 'Pediatric Tumor Immunology' Clinical Cooperation Group (CCG) at the HMGU and at the Schwabing children's hospital of the Klinikum Rechts der Isar (TUM) examined the characteristics and functions of T-cells that recognize EBV-associated tumors in a preclinical model.

Virus-specific T-cells may inhibit or promote tumor growth

Their study demonstrated that different T-cell subsets can affect the growth of EBV-associated tumors in opposite ways. Among the group of T-cells that recognized viral antigens, some inhibited, while others promoted tumor growth. In which respect tumor-promoting and tumor-inhibiting T-cells differ is still unknown and subject of ongoing investigations.

T-cells targeting cellular structures contribute to tumor defense

Besides T-cells recognizing viral components, T-cells targeting cellular structures also effectively inhibited tumor growth. Which antigens these T-cells recognize is currently not known. Presumably, these autoantigens derive from cellular proteins that are expressed after viral infection or cellular transformation. These T-cells, therefore, may contribute to tumor rejection without damaging normal tissue.

"T-cells contribute to the defense against EBV-associated tumors in various and not yet completely understood ways," study leader Behrends summarizes. "But our results show that certain characteristics of the T-cells are crucial for tumor control. This is the starting point for additional studies that aim at improving T-cell-based immunotherapies and to develop vaccines."

By setting up Clinical Cooperation Groups, the Helmholtz Zentrum München is pursuing an interdisciplinary approach to research in order to promote translational research, which means to continue the development of basic science in order to make the results directly exploitable for people. The knowledge transfer between the laboratory and sickbed is brought about through the close cooperation of the scientists at the Helmholtz Zentrum München with the hospitals of the Munich universities and with the Städtisches Klinikum München.

Additional information

* T-cells mediate cellular immune responses. When antigens, i.e. from pathogens or tumor cells, are detected, T-cells begin to differentiate into different effector cells that carry out various defense functions. For example, so-called cytotoxic effector cells kill infected or transformed cells, helper T-cells promote antibody production, and regulatory T-cells suppress excessive immune responses.

Original publication:
Linnerbauer, S. et al. (2014), Virus and Autoantigen-Specific CD4+ T Cells Are Key Effectors in a SCID Mouse Model of EBV-Associated Post-Transplant Lymphoproliferative Disorders, PLOS Pathogens, doi: 10.1371/journal.ppat.1004068

Link to publication

As German Research Center for Environmental Health Helmholtz Zentrum München
pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,200 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 34,000 staff members.

Clinical Cooperation groups at Helmholtz Zentrum München


Scientific contact at the Helmholtz Zentrum München
Prof. Dr. Uta Behrends, Head of Clinical Cooperationgroup „Pediatric Tumor Immunology“ of Helmholtz Zentrums München and of Pediatirc Clinic Schwabing of Klinikums Rechts der Isar of Technischen Universität München, Kölner Platz 1, 80804 München, Tel. +49 89 3068-3076 -