Investigation of cGAS-STING pathway activation and its effects on anti-tumor immune mechanisms

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17606
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Keio University (2022-2023); Tokyo Medical and Dental University (2020-2021)
• Principal Investigator: NIIBE AYANO (樺嶋彩乃) 慶應義塾大学, 医学部(信濃町), 特任助教 (20445448)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: cGAS-STING / 腫瘍免疫

Outline of Final Research Achievements

cGAS-STING, a part of the innate immunity system pathway has been described to provide anti-tumor immune effects. In this project, we aimed to discover the activity and efficacy of its pathway in pancreatic cancer and to propose a novel therapeutic strategy for this dismal disease. Both cGAS and STING expression was observed in approximately 50% of pancreatic cancer cases, suggesting that the signaling was intact. The signal activation and the tissue infiltration ratio of cytotoxic T-lymphocytes were positively correlated, in addition, characteristic differences were also observed in the stromal tissue surrounding the cancer cells corresponding to the presence or absence of the signal. These findings suggest that the characteristics of the cancer-associated fibroblasts might also be involved in the infiltration of cytotoxic T cells and anti-tumor immune effects.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

膵臓癌は一般的に種々の治療に対して抵抗性の性質を有することが知られる。その原因としては、膵癌組織特有の豊富な間質組織が乏血状態を形成し、治療薬剤の局所への到達を妨げていることなどが挙げられているが、本研究課題内で明らかにした膵臓癌症例におけるcGAS-STINGシグナルの有無と細胞傷害性T細胞浸潤比率の相関性はcGAS-STINGシグナルが免疫細胞の癌局所浸潤に関与することだけでなく、癌細胞周囲の特異的間質細胞の存在および特徴もまた腫瘍免疫反応に関与する可能性を示した。
このことは奏功性が低いとされる膵臓癌における癌免疫治療効果改善への足掛かりとなるものと思われる。