PO-373 Dynamics of the esophageal tumour immune micro-environment after neoadjuvant chemoradiation (nCRT)

Abstract

IntroductionIncreasing evidence shows the potential of immunotherapy in several cancers. Little is known about the tumour immune micro-environment of esophageal cancer (EC) in response to conventional nCRT. Here we investigate the tumour immune micro-environment before and after nCRT.Material and methodsAll patients with EC treated with nCRT according to the CROSS regimen between 2004 and May 2013 in the AMC with paired tumour samples available before nCRT, and at surgical resection of the oesophagus, were included. Tumour sections were stained for PD-L1 (clone 28–8, Abcam). Tumours with either partial or circumferential PD-L1 plasma membrane staining, were defined as PD-L1 positive. Positive discordance was defined as a shift from PD-L1 negative to positive; negative discordance as a shift from PD-L1 positive to negative. The immune infiltrate was scored on H and E stained slides, selecting 1 to 5 areas depicting representative immune cell infiltration. Location and PD-L1 expression on tumor-associated immune cells (TAICs) was scored either as intratumoral or peritumoral. Scores were correlated to response to treatment (Mandard score) and survival.Results and discussionsIn total 193 patients with adenocarcinomas (81,3%, n=157) and squamous cell carcinomas (18,7%, n=36) were included. Pre-treatment biopsies were PD-L1 positive in 8.4% of cases (n=15) and showed a significant better histopathological response after nCRT (Mandard 1–3 vs 4–5, p=0.018). Of the post-nCRT resection specimens, 9.7% (n=12) was PD-L1 positive. PD-L1 expression changed after nCRT in 14.5% of the cases, with negative and positive discordance in 8.4% (n=11) and 6.1% (n=8), respectively. If TAICs were present in resection specimens, they displayed more PD-L1 positivity compared to biopsies (42.5% (n=82) vs 23.3% (n=45), p=0.243). In addition, PD-L1 positive TAICs in post-treatment tumours were more often located intratumoral rather than peripheral compared to pre-treatment biopsies, 39.4% (n=76) vs. 22.3% (n=43), respectively.ConclusionPD-L1 positive patients show a significant better response to nCRT. More intratumoral PD-L1 positive TAICs are seen post nCRT, indicating a subset of patients treated with nCRT might benefit from anti-PD-L1 therapy.