SP2 - InCa

Crosstalk between tumor and immune infiltrate

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death. Significant advances have been made in the decoding and therapeutic targeting of tumor cell-autonomous mechanisms of NSCLC tumorigenesis in recent years. In this way, different kinases could be identified and characterized as oncogenic drivers and target structures for therapeutic interventions. The influence of the tumor microenvironment (TME) altered by comorbidities is largely unexplored. In particular, the effect of cigarette smoke-induced chronic airway inflammation (COPD) or obesity is relevant in the context of NSCLC. The influence of these comorbidities on the composition of the TME is particularly relevant with regard to the effectiveness of immunotherapeutics such as immune checkpoint inhibitors (ICI). We have assembled various experimental tools that allow us to study the composition of the TME as a function of major comorbidities such as obesity and COPD. We use genetically modified mouse models (GEMMs) of NSCLC in combination with imaging technologies, insertional mutagenesis screens, metabolic monitoring, mass cytometric TME analysis, multiplex immunohistochemistry and cytokine ELISAs. With these experimental tools we will work on three main questions:
1: Examination of the NSCLC immune infiltrate in the presence or absence of comorbidities.
2: Investigation of tumor cell autonomous effects of the TME.
3: Determining the preclinical effectiveness of ICI in NSCLC in the presence or absence of comorbidities.