Mesothelioma is a relatively rare and invariably fatal pleural malignancy which has a relatively high incidence in Australia due to past mining and use of asbestos products. Our team has been investigating immunotherapy in mesothelioma for over 20 years, with a longstanding focus on chemoimmunotherapy. While dual immunotherapy has recently been demonstrated to improve survival in patients with sarcomatoid and biphasic mesothelioma, the efficacy of this combination in the most common subset, epithelioid mesothelioma, is poor. The potential of chemoimmunotherapy in mesothelioma is supported by mouse model data. More recently, the Australian DREAM and USA PrE0505 clinical trials, which combined chemotherapy with PD-L1 blockade, each achieved their primary endpoints. Results from these trials are being interrogated through translational laboratory work in order to understand the drivers of response; available results from the DREAM study will be presented. This work is progressing to the international randomised phase III DREAM3R clinical trial which will also have an emphasis on translational studies.