Lung cancer – Prof. Ren-Wang Peng, PhD (INSEL) and Prof. Adrian Ochsenbein (INSEL) and Dr. Sabine Schmid (INSEL)

Immunotherapy in malignant pleural mesothelioma

Primary pleural cancers such as the malignant pleural mesothelioma, a lung cancer related to asbestos exposure, are cancers that develop in the chest cavity. Mesothelioma is a devastating cancer of high unmet medical need, and its heterogeneous response to immune checkpoint blockade is the rate-limiting factor for improved treatment.

The project led by Drs. Peng, Ochsenbein and Schmid aims to discover novel immune targets and mechanisms of resistance to immunotherapy in mesothelioma patients. The work builds upon the present state of understanding of mesothelioma treatment, and by determining the variables that correlate with patient response, this study will pave the way for future innovative therapies.

Making use of a large cohort of 109 malignant pleural mesothelioma patients, they will identify the molecular and cellular determinants that correlate with a response to treatments that unblock the patient’s immune response against the tumor. They will use state-of-the-art molecular technologies that visualize the gene expression patterns in the cancer and in the surrounding tissues, cell by cell.

They hope to identify signatures that distinguish responsive from nonresponsive tumors. They will then compare the signature across sections of malignant pleural mesothelioma to determine the effects of the treatments on tumor cell behavior, examining not only the tumor but also the immune cell response to the treatment. To confirm what they will have learned from patient samples, they will then use mouse models of the disease, applying various inhibitors to the mice bearing human mesothelioma. Finally, they will combine immune checkpoint inhibitor therapies with effective inhibitors of growth, both in mouse models and eventually in patients.

The goal is to improve treatments against this devasting disease.