Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma

Apr 14, 2017Oncotarget

Immune cells inside tumors and PD-L1 levels linked to outcomes in esophageal squamous cell cancer

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Abstract

In a study of 428 patients with esophageal squamous cell carcinoma, 79.7% exhibited PD-L1 positivity.

PD-L1 positivity was linked to significantly shorter disease-free survival (DFS) and overall survival (OS) in patients receiving definitive treatment.
No significant correlation was found between PD-L1 expression and progression-free survival (PFS) or OS in the palliative chemotherapy group.
Higher PD-L1 expression was associated with increased density of tumor-infiltrating immune cells (TILs).
In paired tumor samples, an increase in PD-L1 expression correlated with disease progression, while a decrease was linked to response to chemotherapy.
The findings suggest that PD-L1 expression is associated with worse prognosis in esophageal squamous cell carcinoma.

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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.

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Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma

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