The role of immunotherapy in mesothelioma

Malignant pleural mesothelioma (MPM) is a rare tumour occurring after asbestos exposure. Most cases are unresectable at the time of diagnosis and the prognosis is very poor. Platinum based chemotherapy, with or without added antiangiogenics is standard first-line treatment. However, its efficacy is limited, patients with unresectable disease have a median 12 months overall survival and the benefit of treatment is only 3 months. The immune micro-environment plays a crucial role in tumour development. Local immunosuppression involving, but not limited to, the expression of T cell inhibitory receptors, favours tumour growth. Moreover, chronic stromal inflammatory response and the presence of lymphocytic infiltration and macrophages are all prognostic factors. Immune checkpoint inhibitors (ICIs) targeting programmed death protein 1 (PD-1), its ligand (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) are able to block inhibitory signals on T cells, thus enhancing the immune anti-tumour response. PD-L1 is expressed in 60% of MPM and associated with poor prognosis. Several studies have shown encouraging results in single agent or combination checkpoint inhibition in MPM. Furthermore, T cell-mediated treatments are being developed with promising results, as are chimeric antigen receptor (CAR) T cells targeting mesothelin, a highly expressed protein in MPM. In this review, we examine currently available data, as well as ongoing trials in the field of immuno-oncology for MPM.