Elucidation and Control of Pancreatic Cancer Immune Evasion Mechanisms through Single-Cell Analysis of CAF-Cell Interactions.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16424
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Saga University (2022); Kyushu University (2021)
• Principal Investigator: Takesue Shin 佐賀大学, 医学部, 助教 (30883425)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 膵癌 / シングルセル発現解析 / 癌微小環境 / 癌関連線維芽細胞 / 腫瘍免疫

Outline of Final Research Achievements

The aim of this study was to elucidate the changes in the tumor microenvironment during the early stages of pancreatic cancer formation and progression, using single-cell expression analysis of tumor tissue. The study aimed to identify novel cell populations involved in the immune evasion mechanisms of pancreatic cancer cells and establish novel therapeutic strategies to control them.

A mouse model was created by transplanting pancreatic cancer cells derived from spontaneously developed pancreatic cancer in mice, and the impact on the tumor microenvironment by cancer-associated fibroblasts (CAFs) was explored. Co-transplantation with CAFs promoted tumor formation and revealed a reduced infiltration of CD8-positive T cells. Furthermore, morphological classification of organoids derived from surgical specimens of pancreatic cancer revealed a higher dependency on cancer microenvironmental factors secreted by CAFs in well-differentiated pancreatic cancer.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究では膵癌の進展において癌間質中の癌関連線維芽細胞（CAF）が腫瘍抑制的に作用するCD8陽性リンパ球の誘導を抑制することにより膵癌の進展を促進する可能性が示された。
膵癌は極めて予後不良な癌種であり、薬物治療の進歩にも関わらず治療効果は限定的である。本研究の成果により癌関連線維芽細胞を免疫細胞の相互作用が新たな治療標的になる可能性が示唆され、膵癌の薬物治療の進歩を通して社会に貢献できると考えられる。