COMPLEMENT PROTEIN C1Q PRODUCTION IN MALIGNANT PLEURAL MESOTHELIOMA

PURPOSE The complement component C1q has been shown to be abundantly expressed in the microenvironment of several solid tumors where it shows pro-tumor activities (1). We demonstrated that C1q is abundantly present in malignant pleural mesothelioma (MPM), and promote adhesion, migration and invasion of MPM tumor cells. The aim of our study was to investigate the cells and the mechanisms responsible for its local production. METHODS MPM sections were analyzed by immunohistochemistry for the presence of C1q in the microenvironment. MPM human primary mesothelioma cells were isolated from pleural biopsy, characterized by immunofluorescence, cytofluorimetric analysis and their production of cytokines was evaluated by qPCR and ELISA. Human macrophages were incubated with MPM conditioned medium and their phenotype and their production of C1q, was evaluated by qPCR and ELISA. RESULTS C1q was express in tumor-associated stroma of different histotypes of mesothelioma. C1q pattern distribution seems connected to tumor-infiltrating myeloid elements. MPM cells were unable to produce C1q. MΦ treated with MPM conditioned medium have shown an M2-like phenotypic profile (CD206 and IL-10 upregulation) and a significant upregulation in C1q production. No variation was detected for C1s gene. DISCUSSION C1q has been shown able to induce M2-like polarization of Mφ (2). MPM cells increase the C1q production by Mφ. Higher C1q presence in the microenvironment could lead to a stronger M2-like polarization of Mφ producing a self-sustained cycle that could promote tumor malignant progression.CONCLUSIONS C1q fulfill a key role as an immunosuppressive and cancer-promoting factor in mesothelioma microenvironment. BIBLIOGRAPHY 1. Bulla R et al. Nat Commun. 2016 Feb 1;7:10346. 2. Son M et al. Blood. 2016 Nov 3;128(18):2218-2228. (595)