Pleural carcinosis – Dr. Jean Yannis Perentes (CHUV) and Prof. Michal Bassani-Sternberg (UNIL)

Evaluation of the neoantigen-specific T cell response in pleural carcinosis managed by Pressurized IntraThoracic Hyperthermic Aerosol cisplatin Chemotherapy (PITHAC)

Pleural cancer occurs outside the lungs, in the cavity between the lungs and the chest wall that contains a lubricating fluid, as well as along the pleural lining, a membrane surrounding the lungs and lining the chest cavity. Cancer in the pleural cavity has usually spread from somewhere else in the body, most commonly from lung cancer, but it can also come from the breast, ovary, pancreas, colon, or other locations.  Given that pleural tumors are almost always metastatic and difficult to operate, prognosis is poor. One in four patients survives five years after diagnosis of pleural carcinoma. Fortunately, the incidence is low, affecting one in 2’000 cancer patients.

A novel therapeutic approach for pleural carcinoma combines localized, pressurized drug delivery with heat-induced immune stimulation, and goes by the name of PITHAC (pressurized intrapleural hyperthermic aerosol chemotherapy). It is thought that PITHAC triggers a tumor-specific immune response, yet its efficacy in pleural carcinosis remains poorly understood.

This novel project combines a clinician with expertise in the treatment of pleural carcinosis and a biochemical protein analysis expert. The aim is to determine if PITHAC induces novel antigens on the tumor cells, which in turn trigger a neoantigen-specific response in the immune system, notably in T-cells. By determining the antigenic landscape in the tumors of patients with pleural carcinosis, this study will determine if the mode of action of PITHAC includes the induction of a protective neoantigen-specific T-cell response. If so, it would then be reasonable to combine PITHAC with immunotherapies to make them more efficacious.

The researchers will apply this analysis to the patients enrolled in a Phase I clinical trial that started in 2023 at the CHUV (funded by a Chercher-Trouver grant with 750’000 CHF). The trial will assess the feasibility and toxicity of PITHAC in pleural carcinosis patients, and during this trial blood and pleural fluid samples will be collected (after surgery and periodically for a month). The TANDEM grant will finance the analysis of these samples.

The novelty of this project is its longitudinal antigen discovery study, comparing patients before and after therapy, potentially facilitating the integration of PITHAC with immune checkpoint blockade inhibitors and enhancing the study’s translational impact.