Are tumor-infiltrating macrophages derived from monocyte-lineage belonging to the myeloid-derived suppressor cell?

• Project/Area Number: 21590415
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Gifu University
• Principal Investigator: TAKAMI Tsuyoshi 岐阜大学, 医学系研究科, 教授 (70136943)
• Co-Investigator(Kenkyū-buntansha): GOTOH Naoe 岐阜大学, 大学院・医学系研究科, 講師 (80444280) ; KITOH Yusuke 岐阜大学, 大学院・医学系研究科, 助教 (80444305) ; 齊尾 征直 琉球大学, 医学部附属病院, 准教授 (40242721)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: TIM / M1マクロファージ / M2マクロファージ / 骨髄由来サプレッサー細胞(MDSC) / 抗原呈示樹状細胞 / GM-CSF / M-CSF siRNA / 可塑性 / 骨髄細胞由来サプレッサー細胞(MDSC) / tumor associated macrophage / M1 macrophage / M2 macrophage / siRNA / M-CSF receptor / 日ハンガリー科学技術協力 / myeloid-derived suppressor cell / mRNA / Hungary

Research Abstract

The marker profile, production of cytokine and chemokine, and antigen-presenting capability were studied to clarify the origin of tumor-infiltrating macrophages(TIM). Our results clearly showed that TIM was the hetrogeneous cell population having both capabilities of tumor-suppressing(M1) macrophage and tumor-promoting(M2) macrophages. On the other hand, the treatment of TIM with GM-CSF and siRNA for M-CSF induced the intra-cellular signal transducing molecules such as STAT-1, STAT-5, and STAT-6 of which are necessary for maturation toward antigen-presenting dendritic cells, nevertheless the maker-profiles of treated TIM did not change significantly. However both of the GM-CSF and siRNA for M-CSFR treated and non-treated TIM revealed similar antigen presenting capabilities in the system using OVA-specific TCR transgenic mice. Altogether it was clarified that the phenotype of TIM was reflecting the invading tumor microenvironment, and not certain cell type such as myeloid-derived suppressor cells, but was the cell that still keeped plasticity and could be changed by surrounding microenvironment.

Research Products

• [Journal Article] Combined GM-CSF treatement and M-CSF inhibition of tumor-associated macrophages induces dendritic cell-like signaling in vitro (2011)
  • Author(s): Kitoh Y, Saio M, Gotoh N, Umemura N, Nonaka K, Bai J, Vizkeleti L, Torocsik D, Balazs M, Adany R, Takami T
  • Journal Title: International Journal Oncology Volume: Vol.38 Pages: 1409-1419
• [Journal Article] Combined GM-CSF treatment and M-CSF inhibition of tumor-associated macrophages induces dendritic cell-like signaling in vitro (2011)
  • Author(s): Kitoh Y, Saio M, Gotoh N, Umemura N, Nonaka K, Bai J, Vizkeleti L, Torocsik D, Balazs M, Adany R, Takami T
  • Journal Title: International Journal Oncology Volume: 38 Pages: 1409-1419
  • Peer Reviewed