In:
Cancer Science, Wiley, Vol. 107, No. 11 ( 2016-11), p. 1563-1571
Abstract:
To assess the association of the programmed cell death ligand 1 (PD‐L1) with cisplatin‐based neo‐adjuvant chemotherapy (NAC) response, we investigated the level of PD‐L1 and found increased PD‐L1 expression in chemo‐resistant tumors compared with chemo‐sensitive tumors according to RNA‐Seq analysis. In a cohort of 92 patients with NAC , the positive staining of PD ‐ L 1 was correlated with TNM stage, lower sensitive‐response rates and shorter overall survival rates. In another 30 paired tumor specimens pre‐ and post‐chemotherapy, the patients with high PD ‐ L 1 expression post‐chemotherapy had a worse outcome and higher stable disease rate. CD 8 + tumor‐infiltrating lymphocytes were found to be related to chemosensitive response and better prognosis and negative PD ‐ L 1 expression. Furthermore, in two patient‐derived xenograft models and cell lines A 549 and PC ‐9, cisplatin upregulated PD ‐ L 1 expression, and the enhancement of PD ‐ L 1 in cancer cell lines was in a drug dose‐dependent manner. Moreover, the depletion of PD ‐ L 1 significantly reduced cisplatin resistance. When phosphatidylinositol 3‐kinase/protein kinase B signaling was inhibited by corresponding inhibitors, PD ‐ L 1 expression was downregulated and apoptosis was upregulated in the cisplatin‐treated cancer cells. These results suggest that the upregulation of PD ‐ L 1 promotes a resistance response in lung cancer cells that might be through activation of the phosphatidylinositol 3‐kinase/protein kinase B pathway and suppression of tumor‐infiltrating lymphocytes. The high expression of PD ‐ L 1 after NAC could be an indication of therapeutic resistance and poor prognosis in patients with non‐small‐cell lung cancer.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2016.107.issue-11
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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