Professor Kettenmann, were the two conference days a success?
Yes, absolutely. Despite the short duration of the event, we were able to attract a high-quality and very international audience. A total of 36 countries were represented by the speakers and participants. Some of our guests traveled from as far afield as Georgia, India, Korea, and Puerto Rico.
What do you think made this conference so attractive for people?
The unfortunate truth is that we’ve seen little to no progress in the treatment of brain tumors over the past 20 or 30 years. The standard approach to treating a glioma is still operation, radiation, and chemotherapy with the drug temozolomide, and the average survival time for a patient following diagnosis still stands at only 15 months. Scientists are therefore increasingly realizing just how important basic research is in order to better understand the special properties of glioma cells. This is the only way we will be able to treat tumors more effectively in the future. That is why our participants were happy to travel even long distances to attend the conference, as it brought them up to date on the latest advancements in basic research in a short space of time.
What are the most important findings to have come out of this research recently?
First, it’s becoming increasingly clear that that the glioma cells in the brain do not operate in isolation, but interact strongly with the surrounding glial cells. Glial cells make up around half of all human brain cells. It has long been known that tumor cells affect the microglia, leaving these cerebral immune cells less able to attack the malignant tissue. But a new discovery has revealed that another group of glial cells, the star-shaped astrocytes, also transform when in the vicinity of the tumor. At our conference, for example, the prize for the best poster was awarded to one that showed that astrocytes change their phenotype under the influence of tumor cells and ultimately even promote tumor growth.
The cancer cells themselves also seem to be very changeable. What do we currently know about their ability to transform?
There’s a lot of activity in this field of research right now. For example, scientists have started to investigate very systematically how the tumor cells change over the course of the disease. My U.S. colleague Roel Verhaak from the Jackson Laboratory in Farmington, Connecticut, gave a talk at the conference on one of his latest initiatives. He founded the Glioma Longitudinal Analysis (GLASS) Consortium, which involves researchers all around the world collecting and analyzing cancer tissue samples from patients. The plan is to create a large database that will help researchers to better distinguish gliomas from each other in the future. The long-term goal is to offer patients more personalized and thus more effective treatment.
Are there already ways in which differences in gliomas can be detected?
We have a couple. A few years ago, for example, scientists discovered a mutation in the enzyme isocitrate dehydrogenase, or IDH for short, that gives patients a better chance of survival. Large centers now conduct routine checks to see if a patient has this genetic mutation. Maria Castro from the University of Michigan Medical School explained at the conference that this mutation alters the tumor’s environment in such a way that the microglia can better identify and destroy the cancerous tissue. Perhaps this discovery will also find therapeutic use in the future.
To what extent do modern sequencing methods help scientists to better characterize glioma cells?
This is another area of research that was discussed at our conference. Mario Suva from Massachusetts General Hospital in Boston spoke about the results of his single cell sequencing experiment. He isolated tumor tissue and examined the sequence information of a few thousand cells from this sample – in other words, he determined the RNA expression pattern of the individual cells. This revealed the enormous diversity of glioma cells, which currently makes fighting them so difficult.
It is presumably also quite difficult to obtain human tissue samples. What role do animal models play in glioma research?
It is becoming increasingly clear that we cannot transfer the results gained from mouse models, for example, one-to-one to humans. This is evident solely from the fact that a mouse with a brain tumor dies after just one month. We are therefore working very hard to obtain better human material for our experiments. Progress here includes the cultivation of small organ-like structures known as organoids. Also, for about two years now we have been able to cultivate microglia from induced pluripotent stem (iPS) cells. These are mature cells that have been reprogrammed in the lab so that they once again exhibit all the properties of stem cells. However, we do not yet know how good the microglia cells grown from these iPS cells really are. This is what we are currently trying to find out.
A few years ago, a team from your research group published a study showing that the microglia of men and women differs in many respects. Is this finding also interesting for research into brain tumors?
Yes. In our experiments, we already take into account whether the sample material we are working with has come from a female or male patient. The fact that 60 percent of patients with a glioma are men already shows us that gender plays a role in this illness. The disease pattern of neurofibromatosis type I, a brain tumor that generally develops in childhood, also differs between girls and boys. My research group is currently conducting systematic investigations into the different ways the tumor microglia changes over the course of the disease in women and men. Perhaps we will be able to present our initial findings at the next Brain Tumor Meeting.
Anke Brodmerkel conducted the interview.