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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
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
Kishuku, Masatoshi Tokushima University
キーワード
Lung cancer
Malignant pleural mesothelioma
PD-1
MDSC
VEGF
資料タイプ
学位論文
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
ISSN
01695002
cat書誌ID
AA10785743
AA11536857
出版者
Elsevier
146
開始ページ
86
終了ページ
96
発行日
2020-05-21
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
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3457号
学位記番号
甲医第1464号
学位授与年月日
2020-09-24
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院