Scientifically this permanent growth arrest is called senescence (2, 3). As complete cancer eradication is normally not feasible, deadly metastases normally result from surviving and regrowing cancer cells. The new data now explain, how immunity and immunotherapies can efficiently control surviving cancer cells and thus protect from cancer and metastases (1, 4).
Fig. 1: In red, the expression of a senescence marker in former proliferating melanoma cells that underwent growth arrest. Here, senescence occurred in the context of melanoma regression induced by a natural anti-melanoma immune response. In brown, pigment bearing cells.
University Hospital Tübingen
„The major goal of cancer therapy is the eradication, if possible of all cancer cells. Yet, we have learned over the past 50 years that some cancer cells survive even the most aggressive, cancer cell-killing therapy. It is assumed that such surviving cancer cell restore the cancer and cause the deadly metastases. This casts doubt on a therapeutic strategies that focus exclusively on cancer cell killing. Therefore, it was repeatedly postulated that, in addition to cancer cell killing, other (immune-) mechanisms are needed to control cancer (5, 6, 7).“ – as summarized by Professor Röcken.
The Tuebingen research team uncovered a critical, so far unknown immune mechanism that allows to permanently paralyze growing cancer cells. They showed for the first time that immune responses can cause a permanent growth arrest in cancers and also in single cancer cells (1). Scientifically this permanent growth arrest is termed senescence (2, 3).
Even under conditions where the immune system cannot kill the cancer, the two cytokines interferon (IFN) and tumor necrosis factor (TNF), may drive cancers into senescence. Thus, senescence induction causes a state, where ‚the cancer sleeps well controlled in his host’. This was first shown in an islet cancer of the pancreas (1, 4).
The same two cytokines, IFN and TNF, can drive a large number of mouse and human cancer cells into senescence. Clinically, this has two major consequences: Immune-induced senescence (figure 1) is obviously a physiological mechanism that contributes to the natural cancer control in humans (1). On the other side, recent data from cancer immune therapy suggest that the therapy is primarily efficient under conditions where the immune therapy causes permanent growth arrest of the metastases (8, 9).
Two mediators that are long known in cancer and infection immunology turn into the focus: interferon (IFN) and tumor necrosis factor (TNF). Many clinicians and researchers tried to destroy cancer and cancer-supplying vessels – like the Tuebingen researchers. Surprisingly, the Tuebingen group found that a certain combination of IFN and TNF protects mice from the development of islet cancers in the pancreas.
In the animals induction of senescence resulted in unexpectedly long protection from cancer (4). Even more important: when isolated from cancer prone animals, the ‘senescent cancer cells’ remained growth arrested without any further therapy, even when transferred into immune deficient, healthy mice. Thus, the senescent cancer cells had lost the aggressive behavior that characterizes cancer and remained well controlled (1).
This new therapeutic strategy offers the opportunity to develop new cancer immunotherapy that should be less aggressive, with relatively few side effects but highly efficient. Professor Rocken: „It is likely that in the future we will not primarily try to destroy cancer with ever more toxic regimen; instead we will focus on strategies that restore the body’s immune control over cancers “.
Media contactEberhard Karls University Tuebingen
Nature (online 04.02.2013). doi:10.1038/nature11824.2. Michaloglou, C. et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720-724 (2005).
7. Röcken, M. Early tumor dissemination, but late metastasis: insights into tumor dormancy. J. Clin. Invest. 120, 1800-1803 (2010).8. Walter S, et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat. Med. 18, 1254–1261 (2012).
9. Brahmer JR, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 366; 2455-2465 (2012).
Dr. Ellen Katz | idw
Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences