Why there is resistance in cancer immunotherapy
So far, only about ten to twenty percent of the immunotherapies used in cancer patients have been successful. Current data show that some of the patients develop resistance to treatment after one to two years. This unfavorable course contributes to the low probability of success. Research by the Medical University of Innsbruck now provides groundbreaking knowledge on this topic. The researchers have deciphered why these resistances develop and thus provide clues for optimizing immunotherapy.
"The interaction between the tumor and the immune system is highly differentiated and complex and still requires a lot of educational work," explains Zlatko Trajanoski, leading bioinformatician at the Biozentrum der Medizin Uni Innsbruck in a press release on the research results. The researchers were able to demonstrate that tumors become genetically more homogeneous in the course of immunotherapy. As a result, the tumor cells are no longer recognized by the immune system and the tumors start to grow again. The results of the research work were published in the journal "Nature Communications".
What role does the homogeneity of a tumor play?
Tests on mice showed the researchers that the genetic diversity of a tumor diminishes in the course of immunotherapy. Thus, those tumor cells that are not attacked by the immune system survived. "Immuneditation involves immuneditation, which means that tumor cells with certain mutations are eliminated, thereby reducing the genetic heterogeneity of the tumor," explains Trajanoski of the new finding. In this case, an interruption of therapy would be advantageous. However, the researchers also discovered tumors in which this homogeneity did not occur. According to Trajanoski, those tumors that have a broad genetic spread are also those where immunotherapy is successful.
Trajanoski reports on the enormous complexity of the topic. The selection of individual immunotherapies is a special challenge that requires support from bioinformatics. "In order to now be able to predict resistance developments, a comprehensive analysis of the tumor sample should be carried out for its genetic heterogeneity, which would ultimately allow the therapy to be adjusted in terms of dosage and time management," suggest the scientists around Zlatko Trajanoski.
More studies are needed
The Innsbruck research work was made possible by the support of the MCBO doctoral program, the Horizon2020 project APERIM and the Tyrolean Cancer Aid. In future studies, extensive analyzes of tumor samples for their genetic diversity will have to be carried out. According to the scientists, this would predict future resistance and the therapy could be adjusted accordingly. (vb)