Macrophage immune checkpoint dual mechanism in pancreatic cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08779
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyushu University (2022-2023); Ehime University (2021)
• Principal Investigator: Iwamoto Chika 九州大学, 医学研究院, 助教 (10752842)
• Co-Investigator(Kenkyū-buntansha): 大内田 研宙 九州大学, 医学研究院, 准教授 (20452708)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膵癌 / 腫瘍免疫微小環境 / マクロファージ

Outline of Final Research Achievements

Pancreatic cancer is less likely to respond to immune checkpoint inhibitors because of its low expression of PD-L1 and neoantigen and poor immune cell infiltration into the tissue. On the other hand, although strong responses have been reported in hematological malignancy due to the regulation of macrophage immune checkpoints, effective macrophage immune checkpoint molecules and their mechanisms of action in pancreatic cancer have not been elucidated to date. Therefore, we sought to elucidate the mechanism of maintenance of the pancreatic cancer immune microenvironment by the macrophage immune checkpoint. It was suggested that intratumor bacteria increased by NAC promote cancer progression by altering immune cell infiltration into the tumor and macrophage phenotype and phagocytic functions.

Free Research Field

腫瘍免疫学、分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

膵癌において、NACにより増加した腫瘍内細菌が腫瘍内に浸潤する免疫細胞のphenotypeや機能を変化させることで、癌進展を促す可能性があることを見出した。これにより腫瘍浸潤免疫細胞の機能を変化させることで、腫瘍免疫微小環境を改変させ、持続的な抗腫瘍効果が期待できる治療戦略に役立つ成果であり、学術的意義が高いと言える。また、腫瘍内細菌に着目した膵癌患者における新たな治療戦略の道を切り開くことになる可能性があり、社会的意義も大きい。