Regulation of the tumor malignant potentials and immune evasion by CD70-positive stromal cells.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07410
• 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: Nagoya City University
• Principal Investigator: Inaguma Shingo 名古屋市立大学, 医薬学総合研究院(医学), 教授 (80410786)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CD70 / Cancer stroma

Outline of Final Research Achievements

In the present study, the researchers established colorectal cancer (CRC) tissue arrays containing 270 CRC cases. Immunohistochemical analyses using tumor tissue arrays identified the prognostic significance of PBK, PHH3, SPATA18, and p53expressions in CRC cells. Furthermore, the significance of the CD47 expression in tumor-associated macrophage and periostin expression in colorectal cancer-associated fibroblasts were identified. In vitro studies identified the communication between cancer cells and periostin-positive fibroblasts.
In pleural mesothelioma, patients with CD70- and PD-L1-positive tumors showed the worst clinical outcome. In vitro experiments identified that CD70 and PD-L1 cooperatively accelerated the migration and invasion of mesothelioma cells.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

本研究では、腫瘍細胞、腫瘍間質双方に着目し、大腸癌細胞におけるPBK、ヒストンH3、またミトコンドリアのquality controlを行うといわれているSPATA18発現の臨床病理学的重要性とともに、p53発現症例が化学療法に対する反応性が良い可能性も明らかにした。腫瘍間質成分に関しては、マクロファージチェックポイント分子CD47の重要性や、大腸癌間質細胞に発現するperiostinの重要性も明らかにした。一方で、胸膜中皮腫細胞におけるCD70発現は、PD-L1と協調してその浸潤・遊走能、細胞増殖能、免疫逃避を制御するも明らかにした。今後、これらの分子を標的とした新規治療法の確立が望まれる。