2022 Fiscal Year Final Research Report
Molecular Pathological Basis in Salivary Duct Carcinoma from the Perspective on the Establishment of a New Personalized Treatments: A Large-Scale Multi-institutional Study.
| Project/Area Number |
20K07417
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
多田 雄一郎 国際医療福祉大学, 医学部, 准教授 (70292430)
平井 秀明 東京医科大学, 医学部, 助教 (00770744)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 唾液腺導管癌 / androgen receptor / HER2 / 治療効果予測因子 / EZH2 / PD-L1 / 免疫チェックポイント阻害薬 / 自律神経 |
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| Outline of Final Research Achievements |
An EZH2-high status in patients with salivary duct carcinoma (SDC) treated with AR-targeted therapy was associated with a significantly shorter progression-free and overall survival as well as a lower objective response rate and clinical benefit rate. A high expression of EZH2 in SDC might be a predictor of a poor efficacy of AR-targeted therapy.
Upon analyzing the immune microenvironment, an elevated expression of CD8, FOXP3, PD1, PD-L1, CTLA4, and LAG3 was associated with more aggressive histological features and poor prognosis.
We also examined the relationship between the presence of autonomic nerves within the tumor and the prognosis. The presence of TH-positive sympathetic nerves or VAChT-positive parasympathetic nerves were negative prognostic indicators. Notably, cases where both TH and VAChT were expressed in the same nerve indicated an even greater tendency towards a negative prognosis.
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| Free Research Field |
人体病理学（特に唾液線腫瘍）
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| Academic Significance and Societal Importance of the Research Achievements |
我々はSDCに対してアンドロゲン遮断療法（抗AR療法）と抗HER2療法を施行し高い奏効率を得たが、治療効果予測因子は不明であった。また、癌の進展に関与し免疫チェックポイント阻害（ICI）療法の治療効果予測因子としても注目されている癌免疫微小環境や、予後との関連が示唆されている自律神経の役割についても、本腫瘍では不明であった。
本検討でSDCの治療効果予測因子および癌免疫微小環境と自律神経の臨床病理学的意義の一部が明らかになった。これらは、抗AR療法や抗HER2療法、ICI療法、自律神経を標的とした治療法などを含むSDCに対する治療戦略を確立する上での基礎的データになり得る。
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