2022 Fiscal Year Final Research Report
Personalized combination immunotherapy targeting cancer stem cells in oral cancer
Project/Area Number |
19K10292
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 57060:Surgical dentistry-related
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Research Institution | Sapporo Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
中井 裕美 札幌医科大学, 医学部, 研究員 (80792126)
小林 淳一 札幌医科大学, 医学部, 訪問研究員 (80404739)
土橋 恵 札幌医科大学, 医学部, 研究員 (50815264)
宮本 昇 琉球大学, 医学部附属病院, 助教 (80749565)
笹谷 聖 札幌医科大学, 医学部, 研究員 (10815715)
岡本 準也 札幌医科大学, 医学部, 助教 (10749592)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | がん免疫療法 / 口腔がん / 免疫逃避機構 / 免疫チェックポイント阻害薬 / シスプラチン / がん幹細胞特異抗原 |
Outline of Final Research Achievements |
Analyzing the expression levels of immune competent cells at the tumor center (TCe) and the invasive front (IF) of oral squamous cell carcinoma (OSCC), we found the expression of human leukocyte antigen (HLA) class I at the IF and the presence of transcriptional factor FoxP3 T cells in the TCe parenchyma and CD45RO+ T cells in the IF and TCe stroma could be prognostic markers for OSCC. We established multiple HLA-A24-restricted OSCC cell lines and autologous cytotoxic T lymphocyte (CTL) pairs. We identified the olfactory receptor family 7 subfamily C member 1 gene as preferentially expressed in oral cancer stem cells (CSCs), making it a potential candidate for immunotherapy of treatment-resistant CSCs. We demonstrated that treatment with cis-diammine dichloroplatinum (II) enhanced the expression of PD-L1 in OSCC cells, with the HSF1-HSP90 axis playing an important role. These results substantially contribute to combining cytotoxic chemotherapeutics and immunotherapy.
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Free Research Field |
口腔がん
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Academic Significance and Societal Importance of the Research Achievements |
がん特異的免疫応答を誘導するペプチドワクチンの開発はがん免疫療法の根幹をなす重要な課題である。がん幹細胞を標的とした免疫療法の開発や免疫逃避機構の解明など多方面での研究開発を進めることにより、作用機序の異なる複数の免疫療法や化学療法を組み合わせた併用療法の臨床応用が可能になるものと考えられる。
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