Analysis of activation pathways and functional heterogeneity of macrophages - beyond M1/M2 paradigm

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293089
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kumamoto University
• Principal Investigator: TAKEYA MOTOHIRO 熊本大学, 大学院生命科学研究部, 教授 (90155052)
• Co-Investigator(Kenkyū-buntansha): KOMOHARA YOSHIHIRO 熊本大学, 大学院生命科学研究部, 准教授 (40449921) ; OHNISHI KOJI 熊本大学, 大学院生命科学研究部, 助教 (40613378) ; FUJIWARA YUKIO 熊本大学, 大学院生命科学研究部, 講師 (70452886)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: M1/M2マクロファージ / 腫瘍随伴マクロファージ / ヒト悪性腫瘍 / がん幹細胞 / CD163 / CD204 / Stat3 / corosolic acid

Outline of Final Research Achievements

Tumor-associated macrophages of M2-type (M2-TAM) were considered to play an important role in the maintenance of stemness in a human clear cell renal cell carcinoma. In adult T cell leukemia/lymphoma, density of CD163-positive M2-TAM was associated with poor prognosis of patients, whereas CD204-positive M2-TAM was not, indicating the functional difference of CD163-positive TAMs and CD204-positive TAMs.
Increased number of CD169-positive sinus macrophages in the regional lymph nodes of colon cancer and malignant melanoma was associated with favorable prognosis of the patients. Since it is positively correlated with the number of CD8-positive T cells in tumor tissues, CD169-positive sinus macrophages were considered to be involved in the establishment of anti-tumor immunity.
It was found that corosolic acid, a natural compound that suppresses M2-macrophage differentiation, inhibits tumor cell growth via suppressing the Stat3 activation of both tumor cells and macrophages.

Free Research Field

病理学