The role of antigen-presenting CAF for tumor progression in CRC

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16428
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka Metropolitan University (2022); Osaka City University (2021)
• Principal Investigator: Kasashima Hiroaki 大阪公立大学, 大学院医学研究科, 病院講師 (10899678)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 線維芽細胞 / 大腸癌 / 免疫療法

Outline of Final Research Achievements

Background: Antigen-presenting cancer-associated fibroblast (apCAF) is recently reported to be the important CAF subpopulation which regulate tumor immunity. We aim to clarify the role and effect of apCAF for tumor progression in CRCs. Method: Bioinformatic analysis and IHC analysis were performed. Flow cytometry was also performed to isolate apCAF from orthotopic tumor in mouse rectum inoculated with mouse tumor organoid. Result: The apCAF markers were highly upregulated in CAF isolated form human CRCs and metastatic liver tumor compared to normal fibroblast in colon. The prognosis of the CRC patients who have positive expression of apCAF marker was poorer than those who have negative expression of apCAF. The percentage of apCAF in orthotopic rectal tumor in mouse was approximately 26%. Discussion: In CRC, apCAF may stimulate the tumor progression. We will seek to clarify the association between apCAF and tumor immunosuppression.

Free Research Field

癌微小環境

Academic Significance and Societal Importance of the Research Achievements

癌免疫療法は、従来の癌治療と異なり癌の微小環境を標的とした治療法であり、国内外で多数の報告がなされているが、大腸癌の約8割の症例には癌免疫療法の有効性は不良であり、その癌免疫治療抵抗性メカニズムは未だ十分に解明されていない。この研究結果より癌免疫治療抵抗性の原因として癌微小環境、特に線維芽細胞による腫瘍免疫抑制が推察され、今後難治性癌治療において重要な意味を持つと考えられる。