Pleural effusion of patients with malignant mesothelioma induces macrophage-mediated T cell suppression

Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer 2016 July 11 [Link]

Lievense LA, Cornelissen R, Bezemer K, Kaijen-Lambers ME, Hegmans JP, Aerts JG


Clinical studies have demonstrated beneficial effects of immunotherapy in malignant pleural mesothelioma. The pleural cavity seems an attractive compartment to administer these types of therapies, however local immunosuppressive mechanisms could hamper their efficacy. Macrophages are abundantly present within the mesothelioma microenvironment. This study investigates the influence of the macrophage phenotype and their capacity to inhibit local immune responses and the decisive role of pleural effusion (PE) in this regard.
We cultured macrophages in the presence of PEs and investigated their phenotype. Macrophages and T cells were co-cultured in the presence of PEs and tumor cell line supernatants. The levels of 11 cytokines and the prostanoid prostaglandin E2 (PGE2) were measured in PEs and supernatants. The presence and phenotype of macrophages and T cell subsets was measured in the PE of mesothelioma patients.
PE induced a tumor promoting M2 phenotype in macrophages, which was confirmed by the suppressive activity of macrophages on T cell proliferation during co-culture. PGE2 was identified as a potential inducer of the suppressive capacity of macrophages in PE. Macrophages isolated from PEs displayed an M2 phenotype and were negatively correlated with T cells in vivo.
The current study demonstrates that macrophages in PE can play a pivotal role in directly hampering the anti-tumor T cell immune response. This emphasizes the potential of macrophages as a therapeutic target in mesothelioma and indicates that the presence and phenotype of macrophages in PE should be taken into consideration in the application of (intrapleural) immunotherapies.