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Each of these molecules has a membrane-bound receptor form (mPD-L1/mCTLA-4) and a soluble form (sPD-L1/sCTLA-4). However, these prognostic impacts in colorectal cancer (CRC) remain unclear.\nMethods We immunohistochemically scored tumoral mPD-L1/mCTLA-4 expression and quantified preoperative circulatingsPD-L1/sCTLA-4 levels using matched serum specimens from 131 patients with pStage I–III CRC. We also examined the association between these statuses and tumor infiltrating lymphocytes (TILs) in these patients.\nResults Elevated levels of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 were significantly correlated with poor overall survival(OS) and disease-free survival (DFS). Co-high expression of tumoral mPD-L1 and mCTLA-4 or co-elevated levels of serumsPD-L1 and sCTLA-4 were strongly correlated with poor OS and DFS. Multivariate analysis revealed that both statuses were negative independent prognostic factors for OS [hazard ratio (HR) 3.86, 95% confidence interval (95% CI) 1.71–8.51,p = 0.001; HR 5.72, 95% CI 1.87–14.54, p = 0.004, respectively] and DFS (HR 2.53, 95% CI 1.23–4.95, p = 0.01; HR 6.88,95% CI 2.42–17.13, p = 0.0008, respectively). Although low expression of tumoral mCTLA-4 was significantly correlated with increased CD8(+) TILs, there was no correlation in any other combination.\nConclusions We verified the prognostic impacts of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 in pStage I–III CRC patients. 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Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients
http://hdl.handle.net/10076/00019685
http://hdl.handle.net/10076/00019685bb833924-f9b4-4dbc-9c78-810a2d787b22
名前 / ファイル | ライセンス | アクション |
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2020DM0310 (937.4 kB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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公開日 | 2021-06-29 | |||||||||||
タイトル | ||||||||||||
言語 | en | |||||||||||
タイトル | Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients | |||||||||||
言語 | ||||||||||||
言語 | eng | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Tumoral membrane expression | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Soluble receptors and ligands | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | PD-L1 | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | CTLA-4 | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Colorectal Cancer | |||||||||||
資源タイプ | ||||||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
資源タイプ | doctoral thesis | |||||||||||
アクセス権 | ||||||||||||
アクセス権 | open access | |||||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
著者 |
大村, 悠介
× 大村, 悠介
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抄録 | ||||||||||||
内容記述タイプ | Abstract | |||||||||||
内容記述 | Background Programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) play a pivotal role in cancer immunotherapy. Each of these molecules has a membrane-bound receptor form (mPD-L1/mCTLA-4) and a soluble form (sPD-L1/sCTLA-4). However, these prognostic impacts in colorectal cancer (CRC) remain unclear. Methods We immunohistochemically scored tumoral mPD-L1/mCTLA-4 expression and quantified preoperative circulatingsPD-L1/sCTLA-4 levels using matched serum specimens from 131 patients with pStage I–III CRC. We also examined the association between these statuses and tumor infiltrating lymphocytes (TILs) in these patients. Results Elevated levels of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 were significantly correlated with poor overall survival(OS) and disease-free survival (DFS). Co-high expression of tumoral mPD-L1 and mCTLA-4 or co-elevated levels of serumsPD-L1 and sCTLA-4 were strongly correlated with poor OS and DFS. Multivariate analysis revealed that both statuses were negative independent prognostic factors for OS [hazard ratio (HR) 3.86, 95% confidence interval (95% CI) 1.71–8.51,p = 0.001; HR 5.72, 95% CI 1.87–14.54, p = 0.004, respectively] and DFS (HR 2.53, 95% CI 1.23–4.95, p = 0.01; HR 6.88,95% CI 2.42–17.13, p = 0.0008, respectively). Although low expression of tumoral mCTLA-4 was significantly correlated with increased CD8(+) TILs, there was no correlation in any other combination. Conclusions We verified the prognostic impacts of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 in pStage I–III CRC patients. Dual evaluation of immune checkpoint molecules in primary tissues or preoperative serum could identify a patient population with poor prognosis in these patients. |
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言語 | en | |||||||||||
内容記述 | ||||||||||||
内容記述タイプ | Other | |||||||||||
内容記述 | 本文/Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences,Mie University Graduate School of Medicine, 2‑174 Edobashi, Tsu, Mie 514‑8507, Japan | |||||||||||
内容記述 | ||||||||||||
内容記述タイプ | Other | |||||||||||
内容記述 | 16p | |||||||||||
書誌情報 |
発行日 2021-03-25 |
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DOI | ||||||||||||
識別子タイプ | DOI | |||||||||||
関連識別子 | 10.1007/s00262-020-02645-1 | |||||||||||
フォーマット | ||||||||||||
内容記述タイプ | Other | |||||||||||
内容記述 | application/pdf | |||||||||||
著者版フラグ | ||||||||||||
出版タイプ | VoR | |||||||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
出版者 | ||||||||||||
出版者 | 三重大学 | |||||||||||
出版者(ヨミ) | ||||||||||||
ミエダイガク | ||||||||||||
学位名 | ||||||||||||
学位名 | 博士(医学) | |||||||||||
学位授与機関 | ||||||||||||
学位授与機関識別子Scheme | kakenhi | |||||||||||
学位授与機関識別子 | 14101 | |||||||||||
学位授与機関名 | 三重大学 | |||||||||||
学位授与年月日 | ||||||||||||
学位授与年月日 | 2021-03-25 | |||||||||||
学位授与番号 | ||||||||||||
学位授与番号 | 甲医学第2050号 | |||||||||||
ノート | ||||||||||||
Cancer Immunology, Immunotherapy (2020) 69:2533–2546に掲載 | ||||||||||||
資源タイプ(三重大) | ||||||||||||
Doctoral Dissertation / 博士論文 |