| RRC ID |
60797
|
| 著者 |
Komura N, Mabuchi S, Shimura K, Yokoi E, Kozasa K, Kuroda H, Takahashi R, Sasano T, Kawano M, Matsumoto Y, Kodama M, Hashimoto K, Sawada K, Kimura T.
|
| タイトル |
The role of myeloid-derived suppressor cells in increasing cancer stem-like cells and promoting PD-L1 expression in epithelial ovarian cancer.
|
| ジャーナル |
Cancer Immunol Immunother
|
| Abstract |
The aim of this study was to investigate the role of myeloid-derived suppressor cells (MDSC) in the induction of cancer stem-like cells (CSC) and programmed death ligand 1 (PD-L1) expression in ovarian cancer. CSC were defined as tumor cells expressing high levels of aldehyde dehydrogenase 1 (ALDH 1). We inoculated G-CSF-expressing or Mock-expressing ovarian cancer cells into mice, and the frequencies of MDSC and CSC in tumors of these models were compared by flow cytometry. To directly demonstrate the role of MDSC in the induction of CSC and the increase in PD-L1 expression, we performed in vitro co-culture. MDSC and CSC (ALDH-high cells) were more frequently observed in G-CSF-expressing cell-derived tumors than in Mock-expressing cell-derived tumors. Co-culture experiments revealed that MDSC increased the number of CSC via the production of PGE2. Moreover, PGE2 produced by MDSC increased tumor PD-L1 expression via the mammalian target of rapamycin (mTOR) pathway in ovarian cancer cells. In an in vitro experiment in which ovarian cancer cells were co-cultured with MDSC, higher expression of PD-L1 was observed in CSC than in non-CSC (ALDH-low cells). Furthermore, by immunofluorescence staining, we found that PD-L1 was co-expressed with ALDH1 in in vivo mouse models. In conclusion, PGE2 produced by MDSC increases the stem cell-like properties and tumor PD-L1 expression in epithelial ovarian cancer. Depleting MDSC may be therapeutically effective against ovarian cancer by reducing the number of CSC and tumor PD-L1 expression.
|
| 巻・号 |
69(12)
|
| ページ |
2477-2499
|
| 公開日 |
2020-12-1
|
| DOI |
10.1007/s00262-020-02628-2
|
| PII |
10.1007/s00262-020-02628-2
|
| PMID |
32561967
|
| MeSH |
Aldehyde Dehydrogenase 1 Family / metabolism
Animals
Antineoplastic Agents, Immunological / pharmacology
Antineoplastic Agents, Immunological / therapeutic use
B7-H1 Antigen / immunology
B7-H1 Antigen / metabolism*
Carcinoma, Ovarian Epithelial / drug therapy
Carcinoma, Ovarian Epithelial / immunology*
Carcinoma, Ovarian Epithelial / mortality
Carcinoma, Ovarian Epithelial / pathology
Cell Line, Tumor
Coculture Techniques
Dinoprostone / metabolism
Female
Granulocyte Colony-Stimulating Factor / genetics
Granulocyte Colony-Stimulating Factor / metabolism
Humans
Mice
Middle Aged
Myeloid-Derived Suppressor Cells / drug effects
Myeloid-Derived Suppressor Cells / immunology*
Neoplastic Stem Cells / immunology*
Neoplastic Stem Cells / metabolism
Ovarian Neoplasms / drug therapy
Ovarian Neoplasms / immunology*
Ovarian Neoplasms / mortality
Ovarian Neoplasms / pathology
Prognosis
Progression-Free Survival
Xenograft Model Antitumor Assays
|
| IF |
5.442
|
| 引用数 |
0
|
| リソース情報 |
| 遺伝子材料 |
pCAmGCSF (RDB01522)
pCAZ 2 (RDB01870) |
| ヒト・動物細胞 |
OV2944-HM-1(RCB1483) |
