Immunosuppressive cells in the tumor microenvironment in colorectal cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16454
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Endo Eisei 福島県立医科大学, 医学部, 博士研究員 (80836271)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 大腸癌 / マクロファージ / 腫瘍微小環境

Outline of Final Research Achievements

We have recently reported a subgroup of microsatellite unstable CRC exhibiting TGFβ-dependent activation of cancer-associated fibroblasts. In the present study, we focused on the significance of immunosuppressive cell populations in CRC subgroups with different prognoses and therapeutic responses, especially to immune checkpoint inhibitors. We found that CRCs showing TGF-responsive stromal activation were associated with M2 macrophage infiltration,　as well as high levels of an immune checkpoint molecule, TIM-3. M2-polarized macrophages and TGFβ treated monocytes showed increased TIM-3 expression, indicating the possibility of anti-TIM-3 therapy in CRC.

Free Research Field

大腸癌

Academic Significance and Societal Importance of the Research Achievements

本研究では、一部の大腸癌において、免疫チェックポイント分子が高発現すること、またその発現制御においてTGFβが関連する可能性を示した。本研究の結果が将来、大腸癌の微小環境の理解と、個別的な免疫療法の可能性に資するものと考える。