Analysis of cancer immune escape by Claudin-9 expression.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07096
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Toru Miyake 滋賀医科大学, 医学部, 講師 (70581924)
• Co-Investigator(Kenkyū-buntansha): 谷 眞至 滋賀医科大学, 医学部, 教授 (60236677)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Claudin-9

Outline of Final Research Achievements

Claudin-9 is a membrane protein and an essential molecule for tight junctions. On the other hand, the association of Claudin-9 with the malignant potential of colorectal cancer and the tumour microenvironment remains unclear. A CT26 cell line overexpressing Claudin-9 (CT26-OE) was established. CT26-OE mice had significantly reduced overall survival after cancer transplantation compared to control CT26-treated mice. Histology showed more extensive lung metastases in CT26-OE-treated mice than in control CT26. Microarray analysis of total RNA from lung metastases revealed a significantly reduced immune response involved in the inflammatory response in the lungs of CT26-OE-treated mice. The number of CD3-positive cells in the lungs of CT26-OE was found to be significantly reduced compared to CT26 controls. These results suggest that Claudin-9 is involved in the suppression of cancer immunity.

Free Research Field

大腸癌

Academic Significance and Societal Importance of the Research Achievements

本研究の結果としてCT26細胞にClaudin（CLDN）9を過剰発現させることで、細胞の遊走と増殖が亢進した。また、CLDN9を過剰発現させたCT26を移植したマウスでは、静脈投与により、肺転移の数を増加させた。肺の組織では、CLDN9が過剰発現した腫瘍では、腫瘍浸潤T細胞の数が有意に減少していた。これらの所見は、大腸癌細胞におけるCLDN9の発現が、in vivoにおいて腫瘍微小環境に影響を与え、免疫系を抑制することを示唆していた。CLDN9は大腸癌の転移を促進し、T細胞浸潤を阻害することで予後に悪影響を及ぼすことから、癌の進行における重要な要素であり、治療の標的となりうると考えられた。