TP3 - InCa
Targeted reprogramming of tumor-immune cell interactions in lung cancer
Lung cancer is one of the most common and deadliest cancers worldwide. There have been some great breakthroughs in the treatment of lung cancer patients in recent years. Unfortunately, there is still not an effective therapy for all lung tumors. In addition, a large number of patients who can be treated effectively initially relapse after some time.
A promising treatment approach that works very well in individual patients is immunotherapy. However, a large number of patients have not yet benefited from this form of therapy because their tumors are resistant to immunotherapeutic agents.
We are interested in the complex relationships and interactions between the human immune system and tumor cells during immunotherapy and treatment with targeted kinase inhibitors. For an in-depth understanding of these interactions, we are using pharmacological studies, functional genomics (including CRISPR-based genome editing), compound screens in cellular models, and validation studies in mouse models.
We are convinced that a deeper understanding of tumor-immune cell interactions will provide important approaches for new, improved forms of therapy for lung cancer patients.
A) Schematic of the humanized mouse model (top) and exemplary histology of low (−), medium (+), and high (++) CD8 T cell infiltration (bottom). Scale bar 100 µm, representative images of in total n = 19 tumors of n = 10 mice. B) Hyperion imaging mass cytometry false-color image of an osimertinib treated tumor from stained for pan-cytokeratin (CK, cyan), CD8 (green), and Granzyme B (red). The overlay of CD8 and red is colored yellow. Scale bar 100 µm, representative image of n = 6 regions. All panels were published in Brägelmann et al., 2021 Nature Communications 12, 5505 (2021). (https://doi.org/10.1038/s41467-021-25728-8)