ID | 118295 |
Title Alternative | 胸部腫瘍において、S-1は腫瘍由来Bv8およびS100A8の制御を介してMDSCを除去しPD-1阻害薬の効果を増強する
|
Author |
Nguyen, Na Thi
Tokushima University
Mitsuhashi, Atsushi
Tokushima University
Tokushima University Educator and Researcher Directory
KAKEN Search Researchers
Ogino, Hirokazu
Tokushima University
Tokushima University Educator and Researcher Directory
KAKEN Search Researchers
Kozai, Hiroyuki
Tokushima University
Yoneda, Hiroto
Tokushima University
Afroj, Tania
Tokushima University
Sato, Seidai
Tokushima University
Tokushima University Educator and Researcher Directory
KAKEN Search Researchers
Nokihara, Hiroshi
Tokushima University
|
Keywords | oncology
immune checkpoint inhibitor
myeloid-derived suppressor cells
S-1
Bv8
S100A8
|
Content Type |
Thesis or Dissertation
|
Description | Myeloid-derived suppressor cells (MDSCs) have been known to play a pivotal role in the induction of immune tolerance, which limits the benefits of immune checkpoint inhibitors (ICIs). Recent studies revealed that several chemotherapeutic agents decreased tumor-infiltrating MDSCs. Therefore, combination therapy with cytotoxic chemotherapeutic agents and ICIs was approved for first-line treatment for lung cancer. However, the impact of chemotherapeutic agents on MDSCs and an optimal partner of ICIs has not been fully investigated in thoracic tumors, including lung cancer and malignant pleural mesothelioma. In the present study, we found that treatment with 5-FU and its oral formulation, S-1, suppressed tumor progression and inhibited the accumulation of MDSCs in thoracic tumor-bearing mice. Tumor-infiltrating T cells and dendritic cells were significantly expanded in S-1-treated mice. 5-FU suppressed the ability of tumor cells to recruit MDSCs, while it did not suppress the survival and differentiation of mouse MDSCs in vitro. We also revealed that 5-FU or S-1 significantly downregulated the expression of tumor-derived Bv8 and S100A8. The knockdown of Bv8 or S100A8 in tumor cells suppressed tumor growth and MDSC recruitment in vivo. Furthermore, in comparison with pemetrexed, administration of S-1 improved the synergistic therapeutic efficacy of anti-PD-1 antibodies with or without carboplatin. Our findings revealed a novel mechanism wherein S-1 primed a favorable tumor microenvironment to provide the rationale for combination therapy with S-1 and ICIs as the optimal therapy for thoracic cancer.
|
Journal Title |
Cancer Science
|
ISSN | 13497006
|
Publisher | Japanese Cancer Association|John Wiley & Sons
|
Volume | 114
|
Issue | 2
|
Start Page | 384
|
End Page | 398
|
Published Date | 2022-10-26
|
Remark | 内容要旨・審査要旨・論文本文の公開
本論文は,著者Na T. Nguyen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。 |
Rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
|
EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
|
TextVersion |
ETD
|
MEXT report number | 甲第3703号
|
Diploma Number | 甲医第1573号
|
Granted Date | 2023-03-23
|
Degree Name |
Doctor of Medical Science
|
Grantor |
Tokushima University
|
departments |
Medical Sciences
University Hospital
|