Björn Lamprecht and Dr. Stephan Mathas (Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch and Charité - Universitätsmedizin Berlin, Germany) have now demonstrated the production of interleukin 21 (IL-21) in the tumor cells of Hodgkin lymphoma. IL-21 promotes the growth of cancer cells and helps them evade immune system detection (Blood*, Vol. 112. N0. 8, 2008, 3339-3347).
Until now IL-21 was thought to be produced only by T cells, another group of immune cells. Blocking IL-21 production could lead to the development of new therapy strategies for Hodgkin lymphoma in the future, according to the researchers in Professor Bernd Dörken's laboratory, who collaborated with researchers at the University Tor Vergata, Rome (Italy).
It was not until 1994, some 160 years after Hodgkin's lymphoma (HL) was first described by the British physician Thomas Hodgkin (1832), that - using molecular biological methods - scientists discovered that the disease originates from the white blood cells, the B cells. They noticed, however, that the malignant Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL) exhibit a phenotype and characteristics that are considerably altered. Although HRS cells are derived from B cells, they have lost the expression of most of the B cell genes due to reprogramming.
The research hypothesis of the just-published paper was that the tumor cells, due to the loss of many B-cell specific genes, need alternative signaling pathways to maintain their malignant growth. As Dr. Mathas explained, "Reprogramming can provide the cells of Hodgkin ymphoma with this survival advantage." Hence, the researchers were searching for factors that normally do not originate from B cells. They found what they were looking for in the gene for the cytokine IL-21.Different Functions of IL-21
Thus, IL-21 stimulates the T cells of the immune system and, for instance, drives cells of the chronic-lymphatic leukemia of the B-cell type (B-CLL) to apoptosis. By contrast, in T-cell leukemias, IL-21 does just the opposite and stimulates malignant growth. For the first time, the researchers from Berlin and Rome were able to show that IL-21 is produced by lymphatic cells originally derived from B cells. IL-21 activates a specific signaling pathway (STAT3), thus up-regulating the expression of a group of specific genes in HRS cells which support the unchecked growth and survival of HRS cells.
On top of that, according to further findings of the researchers, IL-21 activates a protein (MIP-3 alpha) in the HRS cells that attracts a group of T cells to the tumor which suppress the immune system. In the healthy organism, these regulatory T cells keep the immune system in check and prevent excessive immune responses.
In proximity to the HRS cells there are a large number of these regulatory T cells. Attracted by MIP-3-alpha, they can suppress an effective immune defense of the body against the HRS cells. The production of such chemoattractants could, according to the researchers, also be a cause for why Hodgkin lymphoma contains so few tumor cells. They comprise merely 0.1 to one percent of the tissue.
Animal experiments have shown that in immunological diseases like rheumatoid arthritis and lupus erythematosus, a disease accompanied by symptoms such as skin changes and inflammation of blood vessels and joints, these symptoms can be significantly improved if IL-21 is inhibited. "If we could block IL-21 or also MIP-3 alpha in human tumor cells," Dr. Mathas added, "this might be a new therapeutic approach for Hodgkin lymphoma." The present cure rate for the disease - also in its advanced stages - is 80 to 90 percent, particular when chemotherapy is used. However, these therapy regimens might have severe side ffects including the risk of therapy-induced secondary malignancies.
Only recently Dr. Mathas and Dr. Martin Janz were distinguished for their research on Hodgkin ymphoma with the Curt Meyer Memorial Prize of the Berlin Cancer Society.
*Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3 alpha
Björn Lamprecht1,2, Stephan Kreher1,2, Ioannis Anagnostopoulos4, Korinna Jöhrens4, Giovanni Monteleone3, Franziska Jundt1,2, Harald Stein4, Martin Janz1,2, Bernd Dörken1,2 and Stephan Mathas1,2
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin;2Hematology, Oncology and Tumorimmunology, Charité, Medical University Berlin, CVK, Augustenburger Platz 1, 13353 Berlin; 3Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy; 4Institute for Pathology, Charité, Medical University Berlin, CBF, Hindenburgdamm 30, 12200 Berlin, Germany; prepublished online August 6, 2008; DOI 10.1182/blood-2008-01-134783Barbara Bachtler
Good preparation is half the digestion
15.11.2018 | Max-Planck-Institut für Stoffwechselforschung
How the gut ‘talks’ to brown fat
16.11.2018 | Technische Universität München
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly
The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
15.11.2018 | Earth Sciences
15.11.2018 | Physics and Astronomy
15.11.2018 | Physics and Astronomy