SP1 - InCa

Dissecting the cellular components of non-small cell lung cancer

Analysis of cancers requires a fundamental understanding of tumor-intrinsic somatic mechanisms that bring about transformation from normal cells to cancer cells. Furthermore, it is necessary to investigate the interaction of the tumor cell with the surrounding microenvironment in order to record the tumor dynamics and to identify therapeutic approaches. In addition to the usual treatment with chemotherapeutic agents, the use of immune checkpoint inhibitors (ICI) has led to promising and sometimes long-lasting clinical reactions in lung cancer patients in recent years, so that ICI in combination with chemotherapy is now used for the treatment of all patients with non-small cell lung cancer (non-small cell lung cancer, NSCLC). However, a large number of lung cancer patients do not benefit from this therapy, and at present the molecular factors that lead to successful treatment are unknown. The effectiveness of ICI in cancer patients makes it clear that the interaction between the tumor cells and the immune cells inevitably determines the success of the therapy, and that a more detailed characterization of these dynamics is necessary to understand these mechanisms. While much has been studied about the interaction of T cells and cancer cells, little is known about the quantity and quality of the total immune cell infiltrate in non-small cell lung cancer. In addition, the association with specific somatic changes in the cancer genome has been studied only to a limited extent.
For this reason, we plan to characterize the tumor cells and the cellular tumor infiltrate in NSCLC samples in this project in order to relate the type and quantity of the tumor infiltrate to the genomic profile of the tumor. To this end, we are planning genomic analyzes as well as single-cell RNA sequencing and multi-parameter mass cytometry on tumor resections or biospates from NSCLC patients. Complementary to this, we will investigate tumors from a transgenic NSCLC mouse model. The results of these analyzes will give us information about the extent to which the genomic profile influences the tumor infiltrate. We hope to gain a fundamental and mechanistic understanding of the interaction of NSCLC tumor cells with the micro-environment, thus unveiling the molecular factors of ICI effectiveness.