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

Abstract

13 Background: Programmed death-1 receptor (PD-1) and its ligand (PD-L1) play an integral role in the immune response against cancer. This study investigated the prognostic significance of PD-L1 expression and tumor-infiltrating immune cells (TILs) in tumor microenvironment in Chinese patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 428 archival formalin-fixed, paraffin-embedded (FFPE) ESCC samples were collected between 2004 and 2014 from treatment naïve patients with ESCC after surgery or by diagnostic endoscopic biopsy. Expression of PD-L1 was assessed by IHC. The degree of TILs infiltration was evaluated by examining the H&E-stained specimens. Associations of PD-L1 expression and TILs with clinicopathological features were evaluated by non-zero correlation test. Survival distribution was compared by Kaplan-Meier and a log-rank test. The median follow-up time was 34.4 months(0.3-147.1 m). Changes of PD-L1 expression between paired tumor samples, which were collected before and after chemotherapy (2 cycles and 4 cycles or more), were also evaluated. Results: In the entire cohort, 79.7% (341/428) of specimens were PD-L1+ (defined as having ≥ 1% of tumor cell membranes showing ≥ 1+ intensity). In the intent-to-treat group (patients received curative esophagectomy or definitive chemoradiation therapy), PD-L1 positivity was associated with a significantly poorer DFS and OS. Neither PFS nor OS in palliative chemotherapy group presented a significant difference corresponding to PD-L1 expression. Furthermore, PD-L1 expression was positively associated with TIL density. Changes in PD-L1 expression was examined in 17 paired tumor tissues collected before and after treatments. Results showed that an increase in PD-L1 expression was associated with disease progression, a decrease in PD-L1 expression was associated with satisfactory chemotherapy treatment response. Conclusions: PositivePD-L1 expression was associated with a significantly worse prognosis in 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.