Heterogeneity of the desmoplastic stroma of human pancreatic cancer: Clinicopathological significance and molecular chanisms shaping the heterogeneity

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07414
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Keio University
• Principal Investigator: Masugi Yohei 慶應義塾大学, 医学部(信濃町), 講師 (90528598)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 膵がん / 線維芽細胞亜型 / 不均一 / 免疫療法

Outline of Final Research Achievements

Pancreatic cancer is a hard-to-treat cancer. We focused on pancreatic cancer stroma and set out to assess inter- and intratumoral stromal heterogeneity in a large series of clinical tumors. Here, we developed a pixel-by-pixel image analysis system to digitally differentiate and quantify two mutually exclusive fibroblast subpopulations within tumor tissues. Quantitative computation of these principal fibroblast subpopulations, intratumoral collagen, and CD8+ T cells using whole-tissue sections from 215 treatment-naive pancreatic cancers allowed us to identify three distinct stroma types differentially associated with patient outcomes, molecular characteristics and the immunosuppressive tumor microenvironment. Our human tissue-based quantitative analysis likely provides new insights into the clinical importance of stroma-based pancreatic cancer subtyping in facilitating the development of multidisciplinary treatment strategies against this lethal malignancy.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

膵癌の新規治療標的が模索される中で、特に注目されている間質について、多数の膵癌患者組織を客観的データに基づき解析することにより、間質の性格が患者間で大きく異なることが示され、有効な間質治療戦略の実現のためには適切な患者層別化が重要であることが示唆されました。また、免疫治療との併用が有効とされるある標的間質細胞が膵癌における腫瘍免疫の制御に関わる可能性を裏付ける、ヒトにおける初めてのエビデンスを報告しました。