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Transforming potentially resectable advanced esophageal squamous cell carcinoma (ESCC) into resectable ESCC through preoperative induction therapy is an important component of ESCC comprehensive treatment. Immune checkpoint inhibitor (ICI) therapy has been shown to have significant effects in the treatment of advanced ESCC, but its role in the neoadjuvant treatment of potentially resectable ESCC is unclear. This study aims to investigate the safety and effectiveness of camrelizumab combined with chemotherapy in the neoadjuvant treatment of ESCC.We recruited consecutive patients with potentially resectable ESCC who received preoperative camrelizumab in combination with chemotherapy. Data including demographic data, clinicopathological characteristics, neoadjuvant treatment regimens, lesion changes observed by imaging, and surgical details were retrospectively collected through specially designed forms. Toxic effects of neoadjuvant therapy on hematology, gastrointestinal tract, liver, kidney, skin, and thyroid were also collected. Imaging assessments were performed every 1-2 treatment cycles. Follow-up is based on the patient's regular admission to the hospital for examination and treatment, at least 3 months after surgery.A total of 66 patients with locally advanced ESCC were included in this study, including 8 patients with stage II, 29 patients with stage III, and 29 patients with stage IVA. The objective response rate (ORR) of the neoadjuvant immunotherapy combined with chemotherapy was 75.76% (50/66), and no one developed disease progression. A total of 60 patients underwent surgery, and the R0 resection rate was 98.3% (59/60). The pathological complete remission (pCR) rate and the major pathological response (MPR) rate was 6.7% (4/60) and 20% (12/60), respectively. There were 14 cases of treatment-related adverse reactions3, but no perioperative deaths occurred.Neoadjuvant immunotherapy combined with chemotherapy followed by surgical resection may be an available treatment for patients with locally advanced ESCC.

BACKGROUND: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature. METHODS: The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression analysis were applied to identify IRGs and to construct a prognostic signature and nomogram. RESULTS: MiR-3648 was expectedly highly expressed in EA tumor tissues (P=2.6e-8), and related to the infiltration of activated natural killer cells (NK cells) and activated CD4 T lymphocytes (CD4 cells). A total of 70 miR-3648-targeted genes related to immune cell infiltration were identified. Among them, 4 genes (C10orf55, DLL4, PANX2, and NKAIN1) were closely related to overall survival (OS), and were thus selected to construct a 4-gene risk score (RS). The RS had a superior capability to predict OS [area under the curve (AUC) =0.740 for 1 year; AUC =0.717 for 3 years; AUC =0.622 for 5 years]. A higher score was indicative of a poorer prognosis than a lower score [hazard ratio (HR) =2.71; 95% confidence interval (CI): 1.45–5.09; P=0.002]. Furthermore, the nomogram formed by combining the RS and the TNM classification of malignant tumors (TNM stage) improved the accuracy of survival prediction [Harrell’s concordance index (C-index) =0.698]. CONCLUSIONS: MiR-3648 may play a critical role in EA pathogenesis. The novel 4-gene signature may serve as a prognostic tool to manage patients with EA.