Development of novel classification of colorectal cancer for immunotherapy

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670581
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: National Cancer Center Japan (2015); Osaka University (2014)
• Principal Investigator: Nishikawa Hiroyoshi 国立研究開発法人国立がん研究センター, 先端医療開発センター, 分野長 (10444431)
• Co-Investigator(Renkei-kenkyūsha): DOKI Yuichiro 大阪大学, 大学院医学研究科, 教授 (20291445) ; HONDA Kenya 理化学研究所, 統合生命医科学研究センター, チームリーダー (60334231)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 免疫学 / 制御性T細胞 / 大腸癌

Outline of Final Research Achievements

Human FOXP3+CD4+ T cells were composed of three distinct subpopulations: CD45RA+FOXP3lo+ naive Tregs, CD45RA-FOXP3hi+ effector Tregs, and CD45RA-FOXP3lo+ non-Tregs. While FOXP3+ T cell infiltration is a poor prognosis marker in many cancers, the significance of FOXP3 T cells in colorectal cancers(CRC) has been controversial. While CRC were commonly infiltrated by suppression-competent FOXP3hi Treg cells,they were divided into two groups by the degree of additional infiltration of FOXP3lo non-suppressive T cells. Such cells were induced by IL-12 and TGF-B and were correlated with tumor invasion of intestinal bacteria. Functionally distinct subpopulations of tumor-infiltrating FOXP3+ T cells oppositely contribute to determining CRC prognosis. Depletion of FOXP3hi Treg cells from tumor tissues to augment anti-tumor immunity can be an effective treatment of CRC and other cancers, while strategies to locally increase FOXP3lo non-Treg cells could be tumor-suppressive and -preventive.

Free Research Field

腫瘍学　免疫学