Functional analysis of hypoxia and Hypoxia inducible factor in tumor-immune respose of head and neck cancers

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09762
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Keio University
• Principal Investigator: Ozawa Hiroyuki 慶應義塾大学, 医学部(信濃町), 教授 (30327621)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 頭頸部癌 / 低酸素応答因子 / 腫瘍免疫

Outline of Final Research Achievements

Upon cultivating head and neck carcinoma cells under hypoxic conditions, we observed an augmentation in HIF1-α expression in certain cells, which was accompanied by a concomitant elevation in PD-L1 expression, a key modulator of the immune response. The use of a HIF1-α inhibitor suppressed this heightened expression, suggesting that hypoxic conditions or elevated HIF1-α expression may be instrumental in regulating PD-L1 expression. We are currently investigating the correlation between HIF1-α and PD-L1 expression in surgical specimens. Furthermore, our analysis using TCGA data indicated that the expression of PD-L1 was notably higher in the group with high HIF1-α expression, suggesting the potential for HIF1-α expression to modulate the expression patterns of other immune-related genes.

Free Research Field

頭頸部癌

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、頭頸部癌に対してHIF1-α阻害薬と免疫チェックポイント阻害薬と併用することにより治療効果が増強される可能性を示した。将来の新規治療を開発するための基礎的なデータとなる。これまで頭頸部癌転移において、低酸素が免疫機構に与える影響ついて検討した報告はほとんどなく、本研究は学術的な独自性が高い。