| Autor: |
Min Luo, Yuhui Xia, Fang Wang, Hong Zhang, Danting Su, Chaoyue Su, Chuan Yang, Shaocong Wu, Sainan An, Suxia Lin, Liwu Fu |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Acta Pharmaceutica Sinica B, Vol 11, Iss 10, Pp 3120-3133 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2211-3835 |
| DOI: |
10.1016/j.apsb.2021.03.010 |
| Popis: |
ERK pathway regulated the programmed death ligand-1 (PD-L1) expression which was linked to the response of programmed death-1 (PD-1)/PD-L1 blockade therapy. So it is deducible that ERK inhibitor could enhance the efficacy of PD-1 inhibitor in cancer immunotherapy. In this study, PD0325901, an oral potent ERK inhibitor, strongly enhanced the efficacy of PD-1 antibody in vitro and in vivo models in non-small cell lung carcinoma (NSCLC) cells. Mechanistically, PD0325901 or shRNA-ERK1/2 significantly downregulated the PD-L1 expression in NSCLC cells and increased the CD3+ T cells infiltration and functions in tumor tissue. There was a positive correlation between the p-ERK1/2 expression and PD-L1 expression in patients with NSCLC. And the patients with low p-ERK1/2 expression were observed a high response rate of PD-1/PD-L1 blockage therapy. Our results demonstrate that PD0325901, an ERK inhibitor, can enhance the efficacy of PD-1 blockage against NSCLC in vitro and in vivo models. And the combination of ERK inhibitor such as PD0325901 and PD-1/PD-L1 blockage is a promising regimen and encouraged to be further confirmed in the treatment of patients with NSCLC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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