number of access : ?
number of downloads : ?
ID 115324
Title Alternative
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
Author
Koyama, Kazuya Tokushima University
Kishuku, Masatoshi Tokushima University
Keywords
Lung cancer
Malignant pleural mesothelioma
PD-1
MDSC
VEGF
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Lung Cancer
ISSN
01695002
NCID
AA10785743
AA11536857
Publisher
Elsevier
Volume
146
Start Page
86
End Page
96
Published Date
2020-05-21
Remark
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。
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3457号
Diploma Number
甲医第1464号
Granted Date
2020-09-24
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
University Hospital