論文 - 詳細
| RRC ID | 72224 |
|---|---|
| 著者 | Yamashita K, Iwatsuki M, Yasuda-Yoshihara N, Morinaga T, Nakao Y, Harada K, Eto K, Kurashige J, Hiyoshi Y, Ishimoto T, Nagai Y, Iwagami S, Baba Y, Miyamoto Y, Yoshida N, Ajani JA, Baba H. |
| タイトル | Trastuzumab upregulates programmed death ligand-1 expression through interaction with NK cells in gastric cancer. |
| ジャーナル | Br J Cancer |
| Abstract |
BACKGROUND:The predictive significance of programmed death ligand 1 (PD-L1) for programmed death 1 (PD-1) inhibitors remains unclear in gastric cancer (GC) due to the dynamic alteration by treatments. We aimed to elucidate the effects of trastuzumab (Tmab) on PD-L1 expression in GC. METHODS:PD-L1 expression was evaluated by multicolour flow cytometry analysis after co-culturing GG cell lines and immune cells with Tmab. IFN-γ in the co-culture experiments was quantified. Immunohistochemistry (IHC) for PD-L1 expression using clinical samples was also performed to confirm PD-L1 alteration by Tmab. RESULTS:PD-L1 expression was significantly upregulated by Tmab in HER2-amplified GC cell lines co-cultured with peripheral blood mononuclear cells (PBMCs). PD-L1 upregulation by Tmab was also observed in the GC cells co-cultured with NK cells in time-dependent manner, but not with monocytes. IFN-γ concentration in conditioned media from co-cultured PBMCs and NK cells with Tmab was significantly higher and anti-IFN-γ significantly suppress the Tmab-induced PD-L1 upregulation. IHC also suggested PD-L1 upregulation after Tmab treatment. CONCLUSIONS:Tmab can upregulate PD-L1 expression on GC cells through interaction with NK cells. These results suggest clinical implications in the assessment of the predictive significance of PD-L1 expression for PD-1 inhibitors. |
| 巻・号 | 124(3) |
| ページ | 595-603 |
| 公開日 | 2021-2-1 |
| DOI | 10.1038/s41416-020-01138-3 |
| PII | 10.1038/s41416-020-01138-3 |
| PMID | 33100329 |
| PMC | PMC7851117 |
| MeSH | Antineoplastic Agents, Immunological / pharmacology* B7-H1 Antigen / drug effects B7-H1 Antigen / metabolism* Cell Communication Cell Line, Tumor Coculture Techniques Culture Media, Conditioned Flow Cytometry Humans Interferon-gamma / metabolism Killer Cells, Natural / drug effects Killer Cells, Natural / metabolism* Leukocytes, Mononuclear / drug effects Leukocytes, Mononuclear / metabolism Receptor, ErbB-2 / antagonists & inhibitors Receptor, ErbB-2 / metabolism Stomach Neoplasms / metabolism* Trastuzumab / pharmacology* Up-Regulation / drug effects |
| IF | 5.791 |
| リソース情報 | |
| ヒト・動物細胞 | NUGC-4(RCB1939) |