title: Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma.
abstract: Programmed death-1 receptor (PD-1) and its ligand (PD-L1) play an integral role in regulating the immune response against cancer. This study investigated the prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating immune cells (TILs) in the tumor microenvironment in Chinese patients with esophageal squamous cell carcinoma (ESCC). Archival formalin-fixed, paraffin-embedded ESCC samples from treatment-naïve patients with ESCC after surgery or by diagnostic endoscopic biopsy were collected between 2004 and 2014. Expression of PD-L1 in ESCC tumor specimens was assessed by immunohistochemistry (IHC), and the degree of TIL infiltration was evaluated by examining hematoxylin and eosin-stained (H&E) specimens. PD-L1+ as defined as ≥1% of tumor cell membranes showing ≥1+ intensity. In 428 patients, specimens from 341 (79.7%) were PD-L1+. In the definitive treatment group (patients who received curative esophagectomy or definitive [chemo-]radiation therapy), PD-L1 positivity was associated with a significantly shorter DFS and OS. In the palliative chemotherapy group exhibited, neither PFS nor OS correlated significantly with PD-L1 expression. PD-L1 expression was positively associated with TIL density. In 17 paired tumor tissues collected before and after treatment, an increase in PD-L1 expression was associated with disease progression, whereas a decrease in PD-L1 expression was associated with response to chemotherapy or disease control. So, PD-L1 expression was associated with a significantly worse prognosis in patients with ESCC. These observations suggest that PD-L1 may play a critical role in ESCC cancer progression and provide a rationale for developing PD-L1 inhibitors for treatment of a subset of ESCC patients.
authors.affiliation: Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, P. R. China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Division of Anatomical Pathology, Department of Pathology & Clinical Biochemistry, Queen Mary Hospital, Hong Kong Special Administrative Region, P. R. China.
authors.forename: Anthony W I
authors.initials: AWI
authors.lastname: Lo
authors.affiliation: Global Early Development, Merck Serono China, Beijing, P. R. China.
authors.forename: Angela
authors.initials: A
authors.lastname: Wong
authors.affiliation: Global Early Development, Merck Serono China, Beijing, P. R. China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, P. R. China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
keywords: PD-L1; TILs; esophageal squamous cell carcinoma; prognostic factor; tumor microenvironment