Abstract 2616: Upregulation of program death ligand 1 expression after a single cycle of chemotherapy is associated with inferior survival in patients with local advanced esophageal squamous cell carcinoma treated with preoperative chemoradiotherapy

Abstract

Abstract Introduction Previous studies have demonstrated that the expression of program death-ligand 1 (PD-L1), a ligand of an immune checkpoint, on cancer cells or on immune cells may have prognostic significance in multiple cancer types including esophageal squamous cell carcinoma (ESCC). We evaluated the expression of PD-L1 and its dynamic changes following one cycle of chemotherapy before standard preoperative chemoradiotherapy (CRT) in a cohort of locally advanced ESCC patients. 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. Paired tumor tissues from endoscopic biopsy before and after the single-cycle chemotherapy were available in 21 patients. Immunohistochemical stain for PD-L1 expression was performed using the Clone SP142 antibody (Spring Bioscience, Pleasanton, CA, USA). The expression of PD-L1 was scored as previously reported. Tumor cells were scored according to percentage of positively-stained cells: TC3≥50%, TC2≥5% and <50%, TC1≥1% and <5%, and TC0<1%; Immune cells: IC3≥10%, IC2≥5% and <10%, IC1≥1% and <5%, and IC0<1%. Results In 21 baseline ESCC tissues, 7 of 19 (37%) exhibited positive PD-L1 expression on tumor cells, and 10 of 21 (48%) exhibited positive expression on immune cells. In 21 ESCC tissues obtained a median of 18 days after initiating chemotherapy, 9 of 18 (50%) and 15 of 21 (71%) demonstrated positive PD-L1 expression on tumor cells and immune cells, respectively. The expression of PD-L1 was significantly increased in post-chemotherapy ESCC tissues compared with baseline tissues (p=0.010); and the increased PD-L1 expression between paired tissues was significant on immune cells (p=0.0056) but did not reach statistical significance on tumor cells (p=0.11). The positive PD-L1 expression in baseline ESCC tissues was correlated with better survival (HR: 0.37, p=0.023). Besides, patients with more increase of PD-L1 expression after chemotherapy had significantly worse survival than those with less (median survival: 19.4 vs 71.20 months, HR: 4.07, p=0.0089). Conclusion PD-L1 expression of ESCC can be up-regulated by chemotherapy. The up-regulation of PD-L1 is associated with poor outcome for locally advanced ESCC patients. (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, Ann-Lii Cheng, Chin-Hung Hsu. Upregulation of program death ligand 1 expression after a single cycle of chemotherapy is associated with inferior survival in patients with local advanced esophageal squamous cell carcinoma treated with preoperative chemoradiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2616. doi:10.1158/1538-7445.AM2017-2616