IMMU-02. PROTEOMIC ANALYSIS IDENTIFIED CECR1 MEDIATED RESPONSE IN MACROPHAGE AND TUMOR ASSOCIATED MACROPHAGE. Issue 2 (22nd June 2018)

• Record Type: Journal Article
• Authors: Zhu, Changbin; Zhao, Yang; Kros, Johan; Cheng, Caroline; Ma, Jie
• Is Part Of: Neuro-oncology. Volume 20:Issue 2(2018)supplement 2
• Page Start: i98
• Page End: i99
• Publication Date: 2018-06-22
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy059.318
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Macrophage is of importance in both innate and tumor immunity. In malignant cancers, tumor associated macrophages with various phenotypes are widely distributed. M2-like tumor associated macrophages are capable of promoting tumor development. CECR1, as a defined M2-like TAM expressed protein, promotes M2 macrophage differentiation and promotes glioma development. However, the intracellular alteration by CECR1 in macrophage was remained to be unclear.THP-1 macrophage was knockdowned CECR1 by siRNA in vitro followed by co-stimulation of U87 cells. Cell lysate was analyzed by (nano)LC-MS. Significantly altered proteins were defined by P value< 0.05 followed by pathway analysis using STRING, Cytoscape. Key molecules were validated by real-time PCR and western blot at both transcription and translation level. In THP-1 macrophage, 67 proteins were enriched in cells with CECR1 knockdown which were mapped into three major pathways that most relevant to macrophage functions such as MHC I antigen presentation, Phagosome maturation and Endocytosis. U87 cells mediated macrophage response to CECR1 knockdown was related to the proliferation aspect mediated by attenuation of Proteasome formation. Further analysis showed U87 cells down regulated molecules involved in immune response, phagocytosis as well as endocytosis. There were two molecules S100A9, PLAU were down regulated by CECR1 knockdown in macrophages with/without U87 co-culture. LAT2 was the only protein upregulated by CECR1 knockdown in U87 co cultured macrophages which displayed a IL-10 low, IL-12 high M1-like phenotype. Thus, suppressing CECR1 expression in macrophages with/without U87 co-culture favored an anti-tumor phenotype by various approaches. CECR1 in macrophages would be a promising target of tumor immunotherapy.