Expression of TILs and Patterns of Gene Expression from Paired Samples of Malignant Pleural Mesothelioma (MPM) Patients

SIMPLE SUMMARY: Recently immunotherapy has been approved in first line for patients with MPM. However, the benefit of immunotherapy in MPM is modest, and recognizing the immune landscape of this tumor could guide the optimal therapeutic strategy. In some tumors dynamic changes of TILs has been reported after chemotherapy, endocrine therapy and immunotherapy. We investigated the changes in expression of TILs in human MPM tumor tissue using immunohistochemistry and patterns of gene expression from paired samples. We included samples of patients treated with chemotherapy, immunotherapy and patients without any treatment between the samples. In our series, after systemic treatment or at progressive disease we observed a decrease of the number of TILs and a downregulation of the immune-related genes. In patients without any treatment between the samples we found an increase of immune cells. We suggest that the immune system tends to turn off during the evolution of disease of after treatment. ABSTRACT: MPM is an aggressive disease with an immunosuppressive tumor microenvironment, and interest in exploring immunotherapy in this disease has been increasing. In the first line of treatment, the combination of nivolumab and ipilimumab demonstrated an improvement in survival over chemotherapy. The presence of TILs has been recognized as a marker of antitumor immune response to chemotherapy in solid tumors. The aim of our study is to identify the effect of treatment on immune cells and the immune gene profile in MPM. We investigated the changes in expression of TILs in 10 human MPM paired tumor tissues using immunohistochemistry and gene expression analysis from paired untreated and treated samples. In this small series, we demonstrated that during the evolution of disease without any treatment there was an increase in the inflammatory component in tumor samples. After systemic treatment there was a decrease in the number of TILs. We observed that after systemic treatment or disease progression immune gene signatures were suppressed. Our integrated analysis of paired samples with immune profile and genomic changes on MPM suggested that during the evolution of the disease the immune system tends to switch, turning off with treatment.