The role of STING pathway in pancreatic tumor-stroma interactions

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15491
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Yokohama City University
• Principal Investigator: SATO Takeshi 横浜市立大学, 附属病院, 助教 (50806106)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 膵臓癌 / 癌関連線維芽細胞 / STING

Outline of Final Research Achievements

Pancreatic cancer is a disease with a poor prognosis with a 5-year survival rate of less than 10%. Pancreatic cancer is characterized by an extremely rich stroma. We focused on cancer-associated fibroblasts (CAF) in the tumor stroma, and focused on STING pathway, which is a nucleic acid sensor, as a factor responsible for the interaction between cancer cells and stromal cells. We investigated the role of STING pathway in pancreatic cancer stroma by in vitro and in vivo assays. It was suggested that STING agonist stimulated STING in CAF in the tumor stroma and enhanced the expression of cytokines such as INFβ and resulted in tumor suppression in a subcutaneous implantation model of mice. On the other hand, the factors other than STING agonist that activate STING in CAF have not been identified.
As a result, there are still many issues to be STING pathway as a therapeutic target of pancreatic cancer.

Free Research Field

膵臓癌

Academic Significance and Societal Importance of the Research Achievements

今回の検討で，膵癌の間質に豊富に存在する癌関連線維芽細胞（CAF）のSTINGを活性化することで腫瘍抑制効果が得られる可能性が示唆された．しかし，STINGアゴニスト以外にSTINGを活性化する因子を同定することが出来ず，またSTINGアゴニスト自体も腫瘍縮小効果を得るには腫瘍に直接投与する必要があるなど，STINGを膵癌の治療標的とするには課題が残る結果となった．STING経路の活性化はINFβなど腫瘍免疫を活性化するサイトカインの発現を亢進すると考えられ，何らかの方法でCAFのSTINGを活性化することが出来れば，治療標的としての道が開ける可能性があり，今後の検討課題と考える．