Mesothelioma is a cancer of mesothelial origin, often occurring within the pleural cavity around the lungs. Tissue resident memory CD8+ T (TRM) cells have recently been identified as a reservoir of tumour-reactive T cells, and increased frequencies of these cells in tumours correlate with improved outcomes to immunotherapy such as melanoma and lung cancers. However, the role of TRM in patients with mesothelioma is unknown.
In this study, I aim to identify novel biomarkers predictive of improved outcomes by interrogating the molecular profile and T cell repertoire of TRM in pleural effusions (PE) from patients with mesothelioma. PE samples were collected from patients with mesothelioma distinguished by their length of overall survival from sample collection (n=6). PE associated with mesothelioma is an abnormal accumulation of fluid in the chest that is routinely drained for patient comfort. This fluid contains both immune cells and cancer cells, providing a unique ‘window’ into the local tumour microenvironment. Activated and non-activated TRM (CD8+ CD39+ CD69+ CD103+) from PE were index sorted by flow cytometry into a 96-well plate based on 4-1BB expression.
Cells were then processed for parallel single cell RNA sequencing (scRNA-seq) and T cell receptor sequencing (TCR-seq) to identify pathways of T cell activation associated with TRM clonotypes present in the PE sample. This will be the first comprehensive single cell analysis of TRM in patients with mesothelioma to identify novel molecular signatures associated with improved outcomes and lead to novel therapeutic targets for mesothelioma and other types of cancer.