Abstract 2635: Differential prognostic implications of programmed death-ligand 1 expression on tumor cells and tumor-infiltrating immune cells in patients with locally advanced esophageal squamous cell carcinoma treated with preoperative chemoradiotherapy
Authors: Huang Ta-Chen , Liang Cher-Wei , Lin Chia-Chi , Chen Ya-Jhen , Lin Kuan-Ling , Hsu Chih-Hung 
Published: August 2018

Abstract
Introduction
Previous studies have reported inconsistent results on the prognostic implications of program death-ligand 1 (PD-L1) expression for patients with locoregional esophageal squamous cell carcinoma (ESCC). We evaluated the differential prognostic impacts of the PD-L1 expressions on tumor cells and on tumor infiltrating immune cells in a cohort of locally advanced ESCC patients, receiving neoadjuvant chemoradiotherapy (CRT).
Patients and Methods
A cohort of 66 patients of locally advanced ESCC have been enrolled to a phase II clinical trial of a single-cycle chemotherapy (a combination of weekly paclitaxel, cisplatin and 24 hour infusional 5-fluorouracil, 2 week on plus one week off, followed by paclitaxel/cisplatin (TP) -based preoperative CRT and radical surgery. Primary tumor tissues were retrospectively collected for PD-L1 immunohistochemical stain by the Clone SP142 antibody (Spring Bioscience, Pleasanton, CA, USA). The expression of PD-L1 was scored as previously reported. Tumor cells (TCs) were scored according to percentage of positively-stained cells: TC3≥50%, TC2≥5% and &lt;50%, TC1≥1% and &lt;5%, and TC0&lt;1%; Immune cells (ICs): IC3≥10%, IC2≥5% and &lt;10%, IC1≥1% and &lt;5%, and IC0&lt;1%.
Results
PD-L1 expression was evaluable on tumor cells in 49 patients and on immune cells in 51 patients. TC0, TC1, TC2, and TC3 were scored in 27 (55%), 9 (18%), 11 (22%), and 2 (4%) patients, respectively; and IC0, IC1, IC2, and IC3 were in 25 (49%), 9 (18%), 15 (29%), and 2 (4%) patients, respectively. Regression analysis revealed that PD-L1 expressions on TC and IC exhibited different impacts on overall survival (OS): higher PD-L1 expression on TC trended to correlate with worse OS, whereas higher PD-L1 expression on IC trended to correlated with better OS. The median OSs of patients with TC0 and those with TC 1-3 were 52 months and 21 months, respectively, with a hazard ratio (HR) 1.5 (95% confidence interval [CI]: 0.7~3.3; P= 0.27). According to the PD-L1 expressions on TC and IC, patients with TC(+)/IC(+),
TC(+)/IC(-), TC(-)/IC(+), TC(-)/IC(-) exhibited median OSs of 26, 7, 42, and 43 months, respectively. Patients with TC(+)/IC(-) PD-L1 expression had significantly worse OS than other patients (HR: 2.6, P=0.03). Among patients with TC(+) PD-L1 expression, those with IC(-) had significantly worse OS than those with IC (+), too (HR: 2.5, P=0.04).
Conclusion
High PD-L1 expression on TC and low PD-L1 expression on IC associate with inferior prognosis in locally advanced ESCC patients treated with neoadjuvant CRT. (The study was supported by the grant NTUH 104-M2891 and the grant MOST 105-2314-B-002-186-MY3)
Citation Format: Ta-Chen Huang, Cher-Wei Liang, Chia-Chi Lin, Ya-Jhen Chen, Kuan-Ling Lin, Chih-Hung Hsu. Differential prognostic implications of programmed death-ligand 1 expression on tumor cells and tumor-infiltrating immune cells in patients with locally advanced esophageal squamous cell carcinoma treated with preoperative chemoradiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2635.