Upregulation of programmed cell death ligand 1 promotes resistance response in non‐small‐cell lung cancer patients treated with neo‐adjuvant chemotherapy
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....
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Published in | Cancer science Vol. 107; no. 11; pp. 1563 - 1571 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
John Wiley & Sons, Inc
01.11.2016
John Wiley and Sons Inc |
Subjects | |
Online Access | Get full text |
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Summary: | 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‐L1 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‐L1 expression post‐chemotherapy had a worse outcome and higher stable disease rate. CD8+ tumor‐infiltrating lymphocytes were found to be related to chemosensitive response and better prognosis and negative PD‐L1 expression. Furthermore, in two patient‐derived xenograft models and cell lines A549 and PC‐9, cisplatin upregulated PD‐L1 expression, and the enhancement of PD‐L1 in cancer cell lines was in a drug dose‐dependent manner. Moreover, the depletion of PD‐L1 significantly reduced cisplatin resistance. When phosphatidylinositol 3‐kinase/protein kinase B signaling was inhibited by corresponding inhibitors, PD‐L1 expression was downregulated and apoptosis was upregulated in the cisplatin‐treated cancer cells. These results suggest that the upregulation of PD‐L1 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‐L1 after NAC could be an indication of therapeutic resistance and poor prognosis in patients with non‐small‐cell lung cancer.
We explored PD‐L1 was induced in NSCLC patients with chemo‐resistance. PD‐L1 expression was associated with the poor prognosis for NSCLC patients. PD‐L1 expression changed before and after NAC for NSCLC tissues. |
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Bibliography: | Peking University (PKU) 985 Special Fund for Collaborative Research with PKU Hospitals, the Beijing Municipal Administration of Hospitals‘ Clinical Medicine Development Special Fund, the Capital Health Research and Development Special Fund, the National High Technology Research and Development Program of China. Funding Information ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. |
ISSN: | 1347-9032 1349-7006 |
DOI: | 10.1111/cas.13072 |