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Abstract: Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor, and it is urgently needed to develop novel therapeutic strategies including immunotherapy. In this study, we investigated the upregulation of the programmed death ligand 1 (PD‐L1) due to epithelial‐mesenchymal transition (EMT) in ESCC using an in vitro treatment system with the EMT inducer, glycogen synthase kinase (GSK)‐3 inhibitor, and we also analyzed the correlation of EMT and PD‐L1 expression in the clinical tumor samples of both tissue microarray (TMA) samples (n = 177) and whole tissue samples (n = 21). As a result, the inhibition of GSK‐3β induces EMT phenotype with upregulated vimentin and downregulated E‐cadherin as well as increased Snail and Zinc finger E box‐binding homeobox (ZEB)‐1 gene expression. Simultaneously, we showed that EMT‐converted ESCC indicated the upregulation of PD‐L1 at both protein (total and surface) and mRNA levels. Of importance, we showed that EMT‐converted tumor cells have a capability to induce T‐cell apoptosis to a greater extent in comparison to original epithelial type tumor cells. Furthermore, the immunohistochemical stains of ESCC showed that PD‐L1 expression on tumor cells was positively correlated with EMT status in TMA samples (P = .0004) and whole tissue samples (P = .0029). In conclusion, our in vitro and in vivo study clearly demonstrated that PD‐L1 expression was upregulated in mesenchymal type tumors of ESCC. These findings provide a strong rationale for the clinical use of anti‐PD‐1/anti‐PD‐L1 monoclonal antibodies for advanced ESCC patients. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has become a promising treatment strategy for cancer. Immune checkpoint blockade with anti-CTLA4 mAb and anti-PD-1 mAb has demonstrated clear evidence of objective responses including improved overall survival and tumor shrinkage, driving renewed enthusiasm for cancer immunotherapy in multiple cancer types including esophageal squamous cell carcinoma (ESCC). There are several clinical trials using anti-PD1 mAb for ESCC in early phases and the results are currently promising. Results and Conclusions: In this review, recent advances in cancer immunotherapy for ESCC are discussed with particular focus on immune checkpoint inhibitors and cancer vaccine. [ABSTRACT FROM AUTHOR]

Background Recently, endoscopic submucosal dissection (ESD) has been used as a less invasive treatment for superficial esophageal cancer. Additional treatment is often required after non-curative resection to prevent local recurrence and lymph node metastasis. Here, we present the outcomes of various additional treatments for patients with superficial esophageal cancer who underwent ESD. Methods Between 2006 and 2017, we performed ESD in 179 patients (210 lesions) with superficial esophageal cancer and 44 cases resulted in the non-curative resection diagnosed by the pathological examination. Among them, 29 patients received additional treatment, whereas 15 patients with no additional treatment were followed up. Additional treatment included esophagectomy (8 patients), chemoradiotherapy (15 patients), ablation using argon plasma coagulation (4 patients), and chemotherapy alone (2 patients). We examined the clinicopathological characteristics and prognosis of patients in the additional esophagectomy group (S group) and chemoradiotherapy group (CRT group). Results Twenty-three patients with pT1a-MM, pT1b, lymphatic invasion, venous invasion, and positive resection margins (both horizontal and vertical) were divided into two treatment groups. Clinicopathological characteristics of patients in the S and CRT groups were not significantly different. Pathological findings after additional esophagectomy showed one residual tumor and one lymph node metastasis. There were no recurrences in the two groups. There was no statistically significant difference in the 5-year overall survival rate between the S group (87.5%) and the CRT group (93.3%). One patient from the S group died due to respiratory pneumonia, and one patient died due to radiation pneumonia. However, five out of the 15 (33.3%) patients who were followed up with no additional treatment developed recurrence. The 5-year overall survival rate was 40.4%, which was not significantly different from that in the additional treatment group. However, the 5-year relapse-free survival rate (30%) was significantly different from that in the additional treatment group (P  > 0.05). Conclusion Additional treatment is essential after non-curative endoscopic submucosal resection for esophageal cancer. Additional esophagectomy and chemoradiotherapy were both safe and effective in this cohort. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Circulating tumor cells (CTCs) in patients with malignant tumors can be used as a prognostic marker. Recently the existence of mesenchymal CTCs have been detected by new methods. However, it has been not yet clarified how CTCs are associated with the treatment effects in esophageal cancer patients. We assessed CTCs in esophageal cancer patients and investigated the relationship between CTCs and treatment effect. Methods Seven patients who had potential of curative resection have been enrolled and peripheral blood samples (10ml) were collected before and after treatment. All patients received chemotherapy (5-FU and cisplatin) and four patients of them received as neoadjuvant therapy. Other patients received only chemotherapy and radiation therapy without operation. CTCs were analyzed using a Microfluidic Chip devise provide with the Nihon Gene Research Laboratories. This system can isolates CTCs from blood samples, based on their size and deformability differences from blood cells. Phenotypes of CTCs are determined by staining and scanning systems. A previous report revealed that this method had higher sensitivity for CTCs than conventional methods (the Cell Search system) in 61 metastatic breast cancer. Results Treatments effects were stable disease or better in all cases. Multiple CTCs were detected in all cases before treatment. Five patients had epithelial CTCs and others had only mesenchymal CTCs. Total number of CTCs after treatment whose data can be available decreased except for two cases. One patient had no CTC after treatment. Two cases have been currently analyzing. Conclusion CTCs may exist almost all patients of Stage II or more esophageal cancer. Decreasing the number of CTCs after treatment suggests some relationship between CTCs and treatment effect, and the accumulation of more cases is necessary. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]