PO-387 Phenotypic and functional analysis of malignant mesothelioma tumor-infiltrating lymphocytes (TILs)

Introduction Given the growing interest and promising preliminary results of immunotherapy in mesothelioma, it has become important to more fully understand the immune landscape in this tumour. This may be especially important for deciding who might benefit most from checkpoint blockade or agonist antibody therapy. Although the phenotype of tumour infiltrating lymphocytes (TILs) in mesothelioma is being increasingly well described, there is very little functional analysis of mesothelioma TILs. Material and methods Fresh mesothelioma tissue and blood were sampled from patients enrolled in an on-going clinical trial of radical pleurectomy vs. radical pleurectomy and photodynamic therapy (PDT) at our institution. Following processing, single cell suspensions were used for phenotypic using flow cytometry. Functionality of TILs was accessed by measurement of cytokine (IFN-γ production) following overnight anti-CD3 antibody stimulation ex vivo . These data were compared to TILs from early stage lung cancer patients. Results and discussions Flow cytometric analysis of 19 patient samples so far shows that the numbers of CD8-positive TILs are markedly low at around 3%–10% of total live cells. TILs have an effector memory phenotype enriched for CD103 +tissue memory cells, they show high expression of inhibitory receptors PD-1 (25%–80%) and TIGIT (50%–80%), and have an Eomes hi T-Bet low phenotype. Unlike TILs from early stage lung cancers, which are generally able to make cytokines, TILs from advanced stage mesotheliomas show profound hypofunction in their ability to produce IFNγ ( Conclusion Our results show that TILs from mesothelioma tumours are profoundly hypofunctional. Areas of active interest are to determine the mechanisms and best markers of T cell hypofunction. Such information might allow us to understand with TILs might be activated by checkpoint inhibitors. We also plan to correlate T cell function with clinical responses in our trial.