Programmed death‐ligand 1 is prognostic factor in esophageal squamous cell carcinoma and is associated with epidermal growth factor receptor

Abstract

Programmed death‐ligand 1 (PD‐L1) expression either indicates immune inhibitory status or concurrent immune response. Although the relationship between PD‐L1 and clinical outcomes has been studied widely in recent years, its role in prognosis of esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we assessed the significance of PD‐L1 in ESCC and its association with epidermal growth factor receptor (EGFR) and radiation response. We found that PD‐L1 was present both on the surface of tumor cells and tumor‐infiltrating immune cells. Patients with tumor‐infiltrating immune cell PD‐L1 expression had better survival. PD‐L1 expression on immune cells was an independent prognostic factor for patients with ESCC. PD‐L1 expression either on tumor‐infiltrating immune cells or tumor cells was negatively associated with EGFR expression. EGFR/PD‐L1 pairs could separate the survival between EGFR low/PD‐L1 positive and EGFR high/PD‐L1 negative groups. In ESCC cell lines with EGFR high expression, PD‐L1 expression was induced significantly when EGFR signaling was activated by radiation and was dramatically inhibited by an EGFR tyrosine kinase inhibitor. In conclusion, tumor‐infiltrating immune cell PD‐L1 expression is an independent prognostic factor for ESCC, and the association between EGFR and PD‐L1 is vital to determining survival. It is important to consider radiotherapy‐induced imbalance of pro‐tumor and anti‐tumor immune response. A combination of radiotherapy and PD‐L1‐targeted therapy could be a promising therapeutic strategy for ESCC patients.

Prognostic value of PD-L1 in esophageal squamous cell carcinoma: a meta-analysis

“…After screening the titles and abstracts of these articles, we excluded 232 studies because they were duplicate studies or were irrelevant. After reading 25 potentially eligible articles in detail, we finally included 13 studies in this meta-analysis [ 36 – 48 ]. A detailed flowchart of the above screening process is presented in Figure 1 .…”

“…However, the relationship between PD-L1 expression and the prognosis of patients with ESCC remains unclear. Multiple studies have indicated that PD-L1 expression is associated with a significant poor survival outcome [ 38 , 39 , 42 , 44 , 45 , 48 ], while two studies reported the opposite effect [ 40 , 46 ], and the other studies have shown no association [ 36 , 37 , 43 , 47 ].…”

Hypoxia‐inducible factor‐1α and nuclear factor‐κB play important roles in regulating programmed cell death ligand 1 expression by epidermal growth factor receptor mutants in non‐small‐cell lung cancer cells

“…Overexpression of PD‐L1 has been detected in various kinds of human tumors, including NSCLC, and has been reported to be a poor prognostic indicator of overall survival and a predictive marker of good response to new immunotherapy drugs . Some driver gene mutations including EGFR have been reported to be involved in intrinsic regulation of PD‐L1 expression in various tumors, including NSCLC . Epidermal growth factor receptor is a member of the ErbB family of receptor tyrosine kinases.…”

“…27,28 Some driver gene mutations including EGFR have been reported to be involved in intrinsic regulation of PD-L1 expression in various tumors, including NSCLC. 29 Epidermal growth factor receptor is a member of the ErbB family of receptor tyrosine kinases. EGFR mutants promote tumorigenesis of NSCLC by constitutively activating downstream signaling effectors, including PI3K/AKT, RAS/ ERK, and others.…”

Radiotherapy Upregulates Programmed Death Ligand-1 through the Pathways Downstream of Epidermal Growth Factor Receptor in Glioma

“…Radiotherapy is one of main therapeutic strategies for tumor patients, but several studies have proved that RT can induce PD-L1 expression in various human cancers ( Gong et al, 2017 , Zhang et al, 2017 , Hecht et al, 2016 ). As an immune checkpoint, PD-L1 is generally expressed in various human cancers and helps tumor cells escape host immune responses ( Lee et al, 2006 , Cho et al, 2017 ).…”