The up-regulation of PD-L1 promotes the resistant response in non-small cell lung cancer patients with neo-adjuvant chemotherapy

To assess the significance of programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) and its association with cisplatin-based neo-adjuvant chemotherapy (NAC) response. We investigated that PD-L1 was increased in chemo-resistant tumors compared with chemo-sensitive tumors according to RNA-Seq analysis, which was confirmed in the same cohort using IHC. In a cohort of 92 patients with NAC, the positive staining of PD-L1 was correlated with the 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 of post-chemotherapy had a worse outcome and higher stable disease rate. CD8(+) tumor infiltrating lymphocytes (TILs) was found to be related to chemosensitive response and better prognosis and negative PD-L1 expression. Furthermore, in two PDX models and cell lines A549 and PC-9, cisplatin up-regulated 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 the cisplatin resistance. When PI3K/AKT signaling was inhibited by corresponding inhibitors, PD-L1 expression was down-regulated and apoptosis was up-regulated in the cisplatin treated cancer cells. These results suggest that the up-regulation of PD-L1 promotes the resistant response in lung cancer cells that might be through activation of PI3K/AKT pathway and suppression of TILs. The high expression of PD-L1 after NAC could be the indication of therapeutic resistance and poor prognosis of NSCLC patients. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.PubMe