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
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering