Mechanism of Immune Cell Infiltration in the Efficacy of Cancer Immunotherapy for Metastatic Colorectal Cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15533
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Hiroshima University
• Principal Investigator: Yuge Ryo 広島大学, 病院(医), 講師 (70794791)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 免疫チェックポイント / 癌間質 / 大腸癌

Outline of Final Research Achievements

Immunostaining analysis of approximately 100 colorectal cancer specimens showed that intermasses were significantly higher in excluded and desert type cases than in inflamed type cases, and in liver metastasis cases, intermasses were correlated between primary and liver metastases, regardless of phenotype. In the case of liver metastases, the intermasses were correlated between the primary tumor and liver metastases regardless of phenotype. In the mouse model of liver metastasis, the Inflamed liver metastasis model showed a significant antitumor effect of PD-1 monotherapy compared to the control group. On the other hand, in the Excluded type liver metastasis model, the single agent group showed no clear antitumor effect, while the combination group showed significant metastasis inhibition compared to the control group and the single agent group.

Free Research Field

癌間質相互作用

Academic Significance and Societal Importance of the Research Achievements

様々な癌種、特に大腸癌においては免疫チェックポイント阻害剤(ICI)の効果を増強させる有効性の高い併用薬が見出だせていないのが現状である。本研究成果によって、PDGFR阻害剤の投与は、間質量を減少させ免疫細胞を癌蜂巣に浸潤しやすくするだけでなく、癌間質相互作用に作用して転移抑制効果が期待でき、ＩＣＩとの併用効果が確認できたことで、ICI単剤では奏功しなかった転移性大腸癌症例に対する新規治療法の同定につながり、さらに腫瘍免疫におけるCAFの役割や腫瘍免疫細胞浸潤機構の解明が期待できる。