Background/Aim: The aim of this study was to investigate PD-L1 expression and its association with prognosis in esophageal squamous cell carcinoma (ESCC) before and after neoadjuvant chemotherapy . Patients and Methods: Using a database of 69 ESCC patients, we analyzed PD-L1 expression on tumor cells (TCs) and immune cells (ICs), as well as the density of CD8 + tumor-infiltrating lymphocytes (TILs) in pretreatment biopsy specimens-versus-surgical specimens after resection. We determined the prognostic significance of these factors. Results: The fraction of ESCC containing ICs expressing PD-L1 and having a high CD8 + TIL density was significantly increased after neoadjuvant treatment. However, PD-L1 expression on TCs or ICs, and CD8 + TIL density, was not significantly associated with patient survival in ESCC patients. Conclusion: NAC-FP induced PD-L1 expression on ICs and CD8 + TILs in ESCC patients. This finding suggests that PD-1/PD-L1 blockade could be combined with NAC-FP to treat ESCC patients.Esophageal cancer is the sixth most common cause of cancer-related death, with an estimated 572,000 new cases per year, worldwide (1). It is of two main histological types, esophageal squamous cell carcinoma (ESCC) or esophageal adenocarcinoma. In Asia, incidence rates of squamous cell carcinoma are much higher than adenocarcinoma (2).Neoadjuvant chemotherapy (NAC) or chemoradiotherapy followed by esophagectomy has become the standard treatment worldwide for patients with ESCC. The Japan Clinical Oncology Group 9907study showed that NAC consisting of 5-fluorouracil and cisplatin (FP) significantly extended survival in clinical stage Ⅱ/Ⅲ ESCC, but 5-year survival in patients treated with NAC and surgery was still only 54.8% (3). Therefore, additional treatment strategies are needed to improve the poor prognosis for ESCC patients.Recently, immune checkpoint inhibitors (ICI) have yielded breakthrough treatments in several different solid cancers (4-8), including esophageal cancer (9). In order to reliably achieve cures in a greater fraction of patients, perioperative ICI immunotherapy is now being considered. In preclinical models, ICI was shown to be more effective in neoadjuvant, than in the adjuvant form (10). More recently, in the clinical setting, preoperative treatment with a single dose of anti-PD-1 ICI has been shown to be effective in melanoma (11) and non-small-cell lung cancer (NSCLC) (12). In addition, in order to enhance therapeutic efficacy, combination therapies are being enthusiastically tested (13). In ESCC, an in vitro study revealed that FP chemotherapy induced PD-L1 expression ( 14). Based on these findings, it is hypothesized that a combination of FP and anti-PD-1/PD-L1 ICI is a promising preoperative treatment for ESCC. In this context, in order to study the action of this combination therapy, it is important to analyze the immune tumor microenvironment (iTME) after NAC. Previous studies have shown that the status of the iTME as classified by PD-L1 expression and TIL density, might be predictive of a...
