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
Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research