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: Yubo Jiang, Anthony W I Lo, Angela Wong, Wenfeng Chen, Yan Wang, Li Lin, Jianming Xu
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 18 Pg. 30175-30189 (May 02 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28404915 (Publication Type: Journal Article)

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human

Topics

• Adult
• Aged
• B7-H1 Antigen (genetics, metabolism)
• Biomarkers, Tumor
• Carcinoma, Squamous Cell (genetics, immunology, mortality, pathology)
• Esophageal Neoplasms (genetics, immunology, mortality, pathology)
• Esophageal Squamous Cell Carcinoma
• Female
• Follow-Up Studies
• Gene Expression
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Lymphocytes, Tumor-Infiltrating (immunology, metabolism)
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasm Staging
• Prognosis
• Recurrence
• Stromal Cells (metabolism, pathology)
• Tumor Microenvironment (immunology)