Tumor Cell Plasticity in Therapy Resistance

January 18, 2022

Picture: Roberta Turiello


Prof. Dr. Michael Hölzel, Member of the Cluster of Excellence ImmunoSensation2 at the University of Bonn receives project funding of 1.5 million euros provided by the German Cancer Aid.

Cancer cells can constantly change and in this way evade the immune system. Prof. Dr. Michael Hölzel from the Institute of Experimental Oncology at the University of Bonn is developing an immunotherapy against black skin cancer: He wants to use "smart" immune cells to get a grip on the tumor cells that are currently trying to make themselves invisible. German Cancer Aid is funding the project with 1.5 million euros over the next five years as part of its new "Excellence Funding Program for Established Scientists".

Malignant melanoma (black skin cancer) originates from the pigment-forming melanocytes in the skin. "Melanocytes are very important for us to protect our skin and body from the harmful effects of UV radiation," says Prof. Dr. Michael Hölzel, director of the Institute of Experimental Oncology at the University Hospital Bonn. "One characteristic of melanoma is that it tends to metastasize to different sites inside the body early on." Additionally, melanoma cells are able to evade detection and hence elimination by T Cells by changing their molecular appearance. A key goal of Hölzel’s research is to understand the molecular mechanisms that orchestrate tumor cell plasticity. "For many years, together with other research teams, we have been investigating which influences change the appearance of melanoma cells - these include, for example, inflammatory signals in the tumor tissue," says Hölzel.

Cancer cells also change during the course of immunotherapy and evade the immune system. In the project funded by the German Cancer Aid, Hölzel wants to adjust the immunotherapy accordingly, so that its effectiveness lasts longer. Further, the scientist wants to investigate the phenomenon of various differing melanoma cells arising spontaneously, exhibiting a plethora of different surface features. "In the project, we are looking into the question of whether pure chance also plays a role in this - as if the dice decides which characteristics a melanoma cell has," says the Hölzel. If this is the case, how does such molecular dicing work? How may new therapies like tumor vaccines be made less vulnerable to the power of chance?

In recent years, there has been progress in trying to make the immune system "sharp" against black skin cancer tumor cells. "But only a portion of patients benefit, and the disease often comes back," Hölzel says. "This means there is a great need for better therapies that are smarter than the tumor, so to speak."

Michael Hölzel is a member of the Cluster of Excellence "ImmunoSensation2" and the Transdisciplinary Research Units "Mathematics, Modeling and Simulation of Complex Systems" and "Life and Health" at the University of Bonn.

As part of its new "Excellence Funding Program for Established Scientists", German Cancer Aid is funding a total of six particularly innovative, but also "daring" projects ('High Risk - High Gain'). "In this way, we would like to give researchers the necessary financial and time freedom to implement trend-setting ideas for the prevention, diagnosis and treatment of cancer and to break new ground conceptually," says Gerd Nettekoven, Chairman of the Board of German Cancer Aid. "We see this as an opportunity for a substantial gain in knowledge and the potential to decisively advance cancer medicine."


Press release of German Cancer Aid

Prof. Dr. Michael Hölzel
Direktor des Instituts für Experimentelle Onkologie
Universitätsklinikum Bonn
Tel. +49-228-28712170
E-Mail: Michael.Hoelzel(at)ukbonn.de