Functional analysis of a new anti-cancer molecule that promotes anti-tumor immune responses

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09817
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Kyushu University
• Principal Investigator: Kanematsu Takashi 九州大学, 歯学研究院, 教授 (10264053)
• Co-Investigator(Kenkyū-buntansha): 松田 美穂 九州大学, 歯学研究院, 准教授 (40291520) ; 佐野 朋美 九州大学, 歯学研究院, 助教 (50782075) ; 溝上 顕子 九州大学, 歯学研究院, 准教授 (70722487)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん / 腫瘍免疫 / AKTシグナリング / PRIP

Outline of Final Research Achievements

Developments in tumor immunology have focused attention on the development of new cancer therapies that target tumor-associated macrophages (TAMs), which comprise the tumor microenvironment. TAMs are classified into M1 (tumor cytotoxic) and M2 (tumor growth-promoting) types. In cancer immunopathology, the M1/M2 balance tilts toward the M2 type, and TAMs contribute to cancer malignant transformation. Enhanced PI3K/AKT signaling is important for polarization of TAMs to M2 type. In this study, focusing on the function of PRIP, which negatively regulates PI3K/AKT signaling, we found that decreased PRIP expression in TAMs increases M2 polarization of TAMs and promotes malignant transformation of cancer, but the suppression of PI3K/AKT signaling in M2-type TAMs by PRIP has antitumor effects through repolarization to M1-type TAMs. These results suggest that the suppression of PI3K/AKT signaling in M2 TAMs by PRIP has an antitumor effect by repolarizing M1 TAMs.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

がん細胞とTAMによるがん悪性化機構にPI3K/AKTシグナリングが関与することから、悪性度の高いがんでは、TAMのPRIP発現が低下するとM2型TAMへの誘導が亢進し、がん細胞にとって都合が良い腫瘍微小環境の成立が促進されることが、がん悪性化の一端であることが明らかとなった。よって、TAMでのPRIP発現を調節することが新たな制がん戦略となると考えられる。