Researchers are still discovering new characteristics of Hodgkin lymphoma, a common form of cancer of the lymphatic system. The malignant cells are derived from white blood cells (B cells), but have lost a considerable part of the B cell-specific gene expression pattern. The phenotype and the characteristics of Hodgkin lymphoma cells are therefore unique.
Björn Lamprecht and Dr. Stephan Mathas (Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch and Charité – Universitätsmedizin Berlin, Germany) have demonstrated the production of interleukin 21 (IL-21) in the tumor cells of Hodgkin lymphoma. IL-21, a signaling molecule (cytokine) of the immune system, 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
It has only been a few years since IL-21 was discovered in T cells. The function of IL-21, however, varies greatly depending on the kind of cell. In some cell types IL-21 stimulates the body's protection program, which researchers call programmed cell death or apoptosis. Each cell contains this apoptosis program so that it will self-destruct when it is altered or defective. This prevents the defective cell from damaging the entire organism.
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.
IL-21 also activates a chemoattractant for cells which suppress the immune system
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.
Barbara Bachtler | EurekAlert!
ADP-ribosylation on the right track
26.04.2018 | Max-Planck-Institut für Biologie des Alterns
Flavins keep a handy helper in their pocket
25.04.2018 | University of Freiburg
Magnetic resonance imaging, or MRI, is a widely used medical tool for taking pictures of the insides of our body. One way to make MRI scans easier to read is...
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
26.04.2018 | Medical Engineering
26.04.2018 | Power and Electrical Engineering
26.04.2018 | Information Technology