Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer 2016 July 11[Link]
Chéné AL, d’Almeida S, Blondy T, Tabiasco J, Deshayes S, Fonteneau JF, Cellerin L, Delneste Y, Grégoire M, Blanquart C.
Mesothelioma is a rare and aggressive cancer related to asbestos exposure. We recently showed that pleural effusions (PE) from mesothelioma patients contained high levels of the CCL2 inflammatory chemokine. In the present work, we studied the effect of CCL2 contained in mesothelioma samples particularly on monocyte recruitment. Then, we studied the fate of these monocytes in MPM PE and their impact on tumor cell properties.
The implication of CCL2 in monocyte recruitment was evaluated using transmigration assays and a CCL2 blocking antibody. The phenotype of macrophages was determined by flow cytometry and ELISA. Immunohistochemistry was used to support the results. Co-cultures of macrophages with mesothelioma cells were performed to study cancer cell proliferation and resistance to treatment.
We showed that CCL2 is a major factor of monocyte recruitment induced by MPM samples. Macrophages obtained in MPM samples were M2 macrophages (High CD14, high CD163 and IL-10 secretion following activation). CSF-1R/M-CSF pathway is implicated in M2 polarization and high levels of M-CSF were measured in MPM samples compared to benign PE (4.17 ± 2.75 ng/ml and 1.94 ± 1.47 ng/ml, respectively). Immunohistochemistry analysis confirmed the presence of M2 macrophages in pleural and peritoneal mesothelioma. Finally, we showed that M2 macrophages increased mesothelioma cell proliferation and resistance to treatment.
These results demonstrate the implication of CCL2 in MPM pathogenesis and designate M-CSF as a new potential biomarker of MPM. This study also identifies CCL2 and CSF1-R/M-CSF as interesting new targets to modulate pro-tumorigenic properties of the tumor microenvironment.