Resistance formation in the cancer immunotherapy decrypted

Why it comes to the immunotherapy of cancer resistance

So far, only about ten to twenty percent of the immunotherapies used are successful in cancer patients. Recent data shows that some patients develop resistance to treatment after one to two years. This unfavorable course contributes to the low probability of success. A research work by the Medical University of Innsbruck is now providing a groundbreaking insight into this topic. The researchers have deciphered why these resistances form and thus provide clues for the optimization of 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 bioinformatics scientist at the Biozentrum der Medizin Uni Innsbruck in a press release on the research results. The researchers were able to prove that tumors become genetically more homogeneous in the course of immunotherapy. The result is that the tumor cells are no longer recognized by the immune system and the tumors begin to grow again. The results of the research were published in the journal "Nature Communications".

Researchers at the University of Innsbruck are deciphering the reasons for increased resistance in cancer immunotherapy. These findings have the potential to increase the success rate of cancer immunotherapy in the future. (Image: Alexander Raths / fotolia.com)

What role does the homogeneity of a tumor play??

Experiments on mice showed the researchers that in the course of an immunotherapy the genetic diversity of a tumor decreases. Thus survived those tumor cells that are not attacked by the immune system. "Immune therapy involves so-called immune editing, which means that tumor cells with certain mutations are eliminated, thereby reducing the genetic heterogeneity of the tumor," explains Trajanoski. In this case, a therapy interruption would be beneficial. However, the researchers also discovered tumors where this homogeneity did not occur. According to Trajanoski, those tumors that show a broad genetic spread are also those in which immunotherapy is successful.

Special challenges

Trajanoski reports on the enormous complexity of the topic. Even the selection of individual immunotherapies poses a special challenge, which requires the support of bioinformatics. "In order to be able to predict the development of resistance, a comprehensive analysis of the tumor sample for its genetic heterogeneity should be carried out, which would eventually allow an adaptation of the therapy in terms of dosage and time management," suggest the scientists led by Zlatko Trajanoski.

Further studies are required

The Innsbruck research work was made possible by the support of the doctoral college MCBO, the Horizon2020 project APERIM and the Tyrolean Cancer Aid. Future studies will require comprehensive analysis of tumor samples for their genetic diversity. According to the scientists, this would predict future resistance and the therapy could be adapted accordingly. (Vb)