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Indoleamine 2,3-dioxygenase 1 and Programmed Cell Death-ligand 1 Co-expression Predicts Poor Pathologic Response and Recurrence in Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy

1
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou 510060, China
2
Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou 510060, China
3
Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou 510060, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this study.
Cancers 2019, 11(2), 169; https://doi.org/10.3390/cancers11020169
Received: 7 January 2019 / Revised: 30 January 2019 / Accepted: 30 January 2019 / Published: 1 February 2019
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Abstract

This study aimed to investigate the impact of indoleamine 2,3-dioxygenase 1 (IDO1) expression, programmed cell death-ligand 1 (PD-L1) expression, CD8+ tumor-infiltrating lymphocyte (TIL) status, and their combination on pathologic complete response (pCR) and recurrence in esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (CRT). Indoleamine 2,3-dioxygenase 1, PD-L1, and CD8+ TIL statuses were evaluated by immunohistochemical analysis on pre-CRT biopsies of 158 patients. Sixty-eight patients (43.0%) achieved pCR after neoadjuvant CRT and 48 patients (30.4%) developed recurrences after surgery. IDO1 and PD-L1 proteins were co-expressed in 28 patients (17.7%). Indoleamine 2,3-dioxygenase 1 positive patients showed a significantly lower pCR rate than IDO1 negative patients (28.6% vs. 51.0%, P = 0.007). Similarly, PD-L1 high expression was significantly negatively correlated with pCR rate (27.3% vs. 51.5%, P = 0.004). On multivariate analysis, IDO1 expression was an independent prognostic factor for developing recurrences. Stratification analysis revealed that patients with co-expression of IDO1 and PD-L1 were significantly associated with a lower pCR rate and worse recurrence-free survival than those with one or none positive protein. In conclusion, IDO1 and PD-L1 co-expression could predict poor pathologic response and high risk of recurrence in ESCC after neoadjuvant CRT, indicating a subset of patients who may benefit from CRT combined with immunotherapy. View Full-Text
Keywords: esophageal squamous cell carcinoma; neoadjuvant chemoradiotherapy; IDO1; PD-L1; pathologic response esophageal squamous cell carcinoma; neoadjuvant chemoradiotherapy; IDO1; PD-L1; pathologic response
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Zhou, S.; Zhao, L.; Liang, Z.; Liu, S.; Li, Y.; Liu, S.; Yang, H.; Liu, M.; Xi, M. Indoleamine 2,3-dioxygenase 1 and Programmed Cell Death-ligand 1 Co-expression Predicts Poor Pathologic Response and Recurrence in Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy. Cancers 2019, 11, 169.

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