title: 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.
authors.affiliation: Department of Radiation Oncology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Pang
authors.affiliation: Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Departments of Immunology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Cihui
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China.
authors.forename: Shufei
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Radiation Oncology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Radiation Oncology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China.
authors.forename: Zefen
authors.identifier: http://orcid.org/0000-0002-4290-0379
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D060890:B7-H1 Antigen / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D005500:Follow-Up Studies; D006801:Humans; D007107:Immune System / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D060890:B7-H1 Antigen; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor; esophageal squamous cell carcinoma; programmed death-ligand 1; radiation; tumor-infiltrating immune cell