Research and development of innovative therapeutics for treating cancer by reprogramming both tumor malignancy and abnormal immunity

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430122
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: National Cancer Center Japan (2015-2016); Keio University (2014)
• Principal Investigator: Kudo-Saito Chie 国立研究開発法人国立がん研究センター, 研究所, ユニット長 (90424126)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ALCAM / がん転移 / がん幹細胞 / 免疫抑制 / 免疫疲弊

Outline of Final Research Achievements

ALCAM (CD166) is known as a marker that is highly expressed in cancer stem cells (CSCs) and mesenchymal stem cells (MSCs) of human and mice. In this study, we additionally found that ALCAM is highly expressed in immunosuppressors such as Tregs and MDSCs as well as MSCs. We conducted comprehensive research in vitro and in vivo, and revealed that ALCAM plays a functional role not only in immunosuppressive activity of these immunosuppressors on induction of tumor-specific CTLs, but also in stemness including self-renewability and chemoresistance of CSCs and MSCs, and that blocking ALCAM successfully induces anti-tumor immunity enough for eliminating tumors by abrogating the cancer-caused immune dysfunction in murine tumor models. Thus, targeting ALCAM may be a distinct and promising strategy for treating cancer by simultaneously reprogramming both tumor malignancy and abnormal immunity in clinical settings.

Free Research Field

腫瘍免疫、腫瘍生物学