The Immune Microenvironment of Malignant Pleural Mesothelioma: A Literature Review

SIMPLE SUMMARY: Malignant pleural mesothelioma is a rare and aggressive tumour, associated with asbestos exposure. Current therapeutic approaches for malignant mesothelioma are mainly based on systemic chemotherapy with a median overall survival of less than two years. In the setting of immunotherapy development, there is a need to better understand the immune microenvironment of malignant pleural mesothelioma. In this review, we aim to synthetize the recent advances in knowledge on the immune microenvironment of malignant pleural mesothelioma. This literature review shows that the immune microenvironment of malignant pleural mesothelioma is highly heterogeneous and can be considered as mainly immunotolerant or immunosuppressive. Better understanding of this immune microenvironment is particularly relevant to target molecular vulnerabilities and develop new treatment strategies. ABSTRACT: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour with a poor prognosis, associated with asbestos exposure. Nowadays, treatment is based on chemotherapy with a median overall survival of less than two years. This review highlights the main characteristics of the immune microenvironment in MPM with special emphasis on recent biological advances. The MPM microenvironment is highly infiltrated by tumour-associated macrophages, mainly M2-macrophages. In line with infiltration by M2-macrophages, which contribute to immune suppression, other effectors of innate immune response are deficient in MPM, such as dendritic cells or natural killer cells. On the other hand, tumour infiltrating lymphocytes (TILs) are also found in MPM, but CD4+ and CD8+ TILs might have decreased cytotoxic effects through T-regulators and high expression of immune checkpoints. Taken together, the immune microenvironment is particularly heterogeneous and can be considered as mainly immunotolerant or immunosuppressive. Therefore, identifying molecular vulnerabilities is particularly relevant to the improvement of patient outcomes and the assessment of promising treatment approaches.