Elucidation of induction mechanism of tumor immunity in glioma via CCR4

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15266
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Kindai University
• Principal Investigator: Hara Yuta 近畿大学, 薬学部, 講師 (20803779)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: グリオーマ / CCR4 / Th17細胞

Outline of Final Research Achievements

In the present study, I examined the roles of CCR4, one of the chemokine receptors, in the pathology of glioma. CCR4 deficient mice displayed the increase in tumor volume and shortened survival duration compared with wild-type mice. Flow cytometry analysis showed that CCR4 deficiency caused a decrease in Th17 cells, but not Treg and Th2 cells, in the brain. Furthermore, M1 macrophages were decreased in the brain of CCR4 deficient mice. M1 macrophages are known to kill tumor cells in glioma. Similar results were obtained from the experiments using selective CCR4 antagonist Compound22-treated mice. These results suggest that CCR4 would be involved in suppression of tumor growth via migration of Th17 cells and macrophage polarization in glioma.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

他のがん種に比べ、グリオーマは治療薬が極端に少なく、また手術による腫瘍の除去も困難なため、極めて難治性の癌である。また、T細胞を始めとした各種免疫細胞の役割および浸潤機序の解明が、抹消組織に発生したがんと比べ、進んでいない。本課題で見出した知見は、グリオーマにおけるTh17細胞の浸潤機序および役割の解明の一助となると考えている。