| RRC ID |
65469
|
| 著者 |
Okita R, Maeda A, Shimizu K, Nojima Y, Saisho S, Nakata M.
|
| タイトル |
PD-L1 overexpression is partially regulated by EGFR/HER2 signaling and associated with poor prognosis in patients with non-small-cell lung cancer.
|
| ジャーナル |
Cancer Immunol Immunother
|
| Abstract |
Immunocheckpoint inhibitors targeting the programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) axis have shown promising results in patients with non-small-cell lung cancer (NSCLC). Recent research has shown that epidermal growth factor receptor (EGFR) signaling affects PD-L1 expression in NSCLC cells; however, the mechanism regulating PD-L1 expression in tumor cells remains unclear. Using immunohistochemistry, we evaluated the impact of expression of PD-L1 and EGF family receptors EGFR and human epidermal growth factor receptor 2 (HER2) in tumor cells from 91 patients with pathological Stage IA-IIIA NSCLC. Overexpression of PD-L1 was observed in 14% of the resected tumors, and associated with poor recurrence-free survival (p = 0.021) and overall survival (p = 0.033). PD-L1 expression is positively correlated with EGFR expression and inversely correlated with HER2. NSCLC cell lines were treated in vitro with the EGFR ligand EGF with or without inhibition of EGFR or HER2, after which PD-L1 expression was evaluated using flow cytometry. Consistent with previous reports, PD-L1 expression was clearly enhanced by EGF. EGFR-tyrosine kinase inhibitors or EGFR small interfering RNA (siRNA) blocked EGF-induced PD-L1 overexpression in NSCLC cell lines, but HER2 siRNA did not. Moreover, our findings suggest that PD-L1 expression could be partially regulated via the PI3K/AKT and JAK/STAT pathways. We conclude that PD-L1 overexpression is associated with poor prognosis and is positively correlated with EGFR expression but inversely correlated with HER2 expression in NSCLC. We also showed that EGFR and HER2 have different effects on EGF-induced PD-L1 expression in NSCLC cell lines.
|
| 巻・号 |
66(7)
|
| ページ |
865-876
|
| 公開日 |
2017-7-1
|
| DOI |
10.1007/s00262-017-1986-y
|
| PII |
10.1007/s00262-017-1986-y
|
| PMID |
28341875
|
| MeSH |
A549 Cells
Adult
Aged
Aged, 80 and over
B7-H1 Antigen / antagonists & inhibitors
B7-H1 Antigen / genetics
B7-H1 Antigen / metabolism*
Carcinoma, Non-Small-Cell Lung / diagnosis*
Carcinoma, Non-Small-Cell Lung / mortality
Carcinoma, Non-Small-Cell Lung / pathology
Disease-Free Survival
ErbB Receptors / genetics
ErbB Receptors / metabolism*
Female
Flow Cytometry
Humans
Immunohistochemistry
Lung Neoplasms / diagnosis*
Lung Neoplasms / mortality
Lung Neoplasms / pathology
Male
Middle Aged
Molecular Targeted Therapy
Prognosis
RNA, Small Interfering / genetics
Receptor, ErbB-2 / genetics
Receptor, ErbB-2 / metabolism*
Recurrence
|
| IF |
5.442
|
| リソース情報 |
| ヒト・動物細胞 |
A549
LC-2/ad(RCB0440)
RERF-LC-KJ(RCB1313) |
