ID | 115324 |
タイトル別表記 | 抗PD-1抗体への化学療法の併用はmyeloid-derived suppressor cellsを減少させることにより中皮腫の増殖を抑制する
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著者 |
大塚, 憲司
徳島大学大学院医科学教育部(医学専攻)
香西, 博之
Tokushima University
米田, 浩人
Tokushima University
Kishuku, Masatoshi
Tokushima University
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キーワード | Lung cancer
Malignant pleural mesothelioma
PD-1
MDSC
VEGF
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資料タイプ |
学位論文
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抄録 | Background: The combination of anti-PD-1/PD-L1 antibody with chemotherapy has been approved for the first-line therapy of lung cancer. However, the effects against malignant mesothelioma (MPM) and the immunological mechanisms by which chemotherapy enhances the effect of targeting PD-1/PD-L1 in MPM are poorly understood.
Materials and Methods: We utilized syngeneic mouse models of MPM and lung cancer and assessed the therapeutic effects of anti-PD-1 antibody and its combination with cisplatin (CDDP) and pemetrexed (PEM). An immunological analysis of tumor-infiltrating cells was performed with immunohistochemistry. Results: We observed significant therapeutic effects of anti-PD-1 antibody against MPM. Although the effect was associated with CD8+ and CD4+ T cells in tumors, the number of Foxp3+ cells was not reduced but rather increased. Consequently, combination with CDDP/PEM significantly enhanced the antitumor effects of anti-PD-1 antibody by decreasing numbers of intratumoral myeloid-derived suppressor cells (MDSCs) and vessels probably through suppression of VEGF expression by CDDP+PEM. Conclusions: The combination of anti-PD-1 antibody with CDDP+PEM may be a promising therapy for MPM via inhibiting the accumulation of MDSCs and vessels in tumors. |
掲載誌名 |
Lung Cancer
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ISSN | 01695002
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cat書誌ID | AA10785743
AA11536857
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出版者 | Elsevier
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巻 | 146
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開始ページ | 86
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終了ページ | 96
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発行日 | 2020-05-21
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備考 | 内容要旨・審査要旨・論文本文の公開
本論文は, 著者Kenji Otsukaの学位論文として提出され, 学位審査・授与の対象となっている。 |
EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
博士論文全文を含む
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文科省報告番号 | 甲第3457号
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学位記番号 | 甲医第1464号
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学位授与年月日 | 2020-09-24
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学位名 |
博士(医学)
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学位授与機関 |
徳島大学
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部局 |
医学系
病院
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