Researchers at the Med Uni Innsbruck describe mechanisms of resistance to cancer immunotherapy

Cancer immunotherapy is changing the way we treat cancer. Approved drugs target the immune system’s own ability to eliminate tumor cells and combat the cancer. However, only 10-20% of the patients are responding to these drugs. Moreover, recent data show that some of these patients develop resistance to cancer immunotherapeutics after one or two years. Austrian researchers now provide a first explanation for this unfavorable course.
Cancer progression is a complex process. Tumor cells develop very differently depending on their place of origin, genetic makeup or tumor microenvironment and they have numerous mutations. This heterogeneity of the tumor is currently a hot topic in cancer research. A joint research work by APERIM coordinator Zlatko Trajanoski and cell genetics experts of the Medical University of Innsbruck is now providing possible answers on the mechanisms of resistance to cancer immunotherapy. The findings were published recently in Nature Communications.

Heterogeneous versus homogeneous tumor development The researchers were using genetic and immunological methods and were able to demonstrate that tumors become genetically more homogeneous during the course of immunotherapy. Subsequently, the tumor cells are not recognized by the immune system and the tumor grows larger. “During the course of cancer Immunotherapy a so-called immune editing occurs, meaning that tumor cells with certain mutations are eliminated and thereby reducing the genetic heterogeneity of the tumor ,” Trajanoski explains the new finding. Extensive methodology Using an immunodeficient mouse model, researchers were able to distinguish the effects of the immune system from genetic influences. Suprisingly, the tumor development in the mouse model was neutral, ie without positive or negative selection. The findings of the Innsbruck research work are based on a remarkably comprehensive methodology with Next Generation Sequencing technology, immunological characterization and bioinformatics analyzes.

The researchers propose that in order to predict the development of resistance, a comprehensive analysis of the tumor sample for its genetic heterogeneity should be carried out. This could eventually result in an adaptation of the therapy in terms of dosage and time Management.

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