Projekt 4

MOLECULAR ANALYSIS OF CIRCULATING TUMOR CELLS AND EXTRACELLULAR VESICLES IN PATIENTS WITH NON-SMALL CELL BRONCHIAL CARCINOMA OR GLIOBLASTOMA TREATED WITH IMMUNE CHECKPOINT INHIBITORS

Treatment with immune checkpoint inhibitors represents a new effective therapeutic option for cancer patients. A major problem with this treatment is the development of primary and secondary resistance, which is why only about one third of patients benefit from therapy with immune checkpoint inhibitors alone. Both circulating tumor cells (CTCs) and extracellular vesicles (EVs) may play a critical role in mediating resistance. Tumor cells are thought to undergo an evolution from an epithelial to a mesenchymal phenotype, which is often associated with metastasis and with development of resistance to systemic therapies. EVs increasingly play an essential role as mediators of cell-cell communication in this context. In preclinical experiments, Axlein was shown to be master regulator of epithelial-mesenchymal transition, which is also involved in resistance mediation.

The so-called liquid biopsy is much less invasive compared to conventional biopsies and can potentially better map intratumor heterogeneity, which is a cornerstone for secondary resistance. Therefore, the liquid biopsy approach is ideally suited for serial analyses of tumor material and response under ongoing therapy can be better monitored. Since diagnostic leukapheresis (DLA) increases CTC yield, we are using it to obtain a larger number of circulating tumor cells from NSCLC patients for mulit-omics analyses. We will also test whether CTCs can be detected in this way in glioblastoma patients.

CTCs and EVs will be characterized with respect to their expression patterns at the genomic, transcriptomic, and proteomic levels and compared both between patients (response vs. non-response) and between tumor entities.