NRG1 Contributes To PD-L1 Mediated Tumor Immune Evasion In Esophageal Squamous Cell Carcinoma

Objective:To explore the role of neuregulin 1 in promoting tumor immune escape mediated by the expression of PD-L1 in esophageal squamous cell carcinoma,and provide insight for searching novel therapeutic and immune combination therapy.Methods:1.We analyzed the expression differences of NRG1 in esophageal cancer and adjacent normal tissues based on TCGA datasets,and Real-time PCR technology was used to verify the expression level of NRG1 in esophageal squamous cell carcinoma and its relationship with prognosis.2.TCGA data was used to analyze PD-L1 expression difference between esophageal cancer and adjacent tissues and the correlation between NGR1 and PD-L1.Western Blot and Real-time PCR were used to verify the expression of PD-L1 in esophageal squamous cell carcinoma.The expression of PD-L1 was detected after knocking down NRG1 or adding exogenous recombinant human NRG1 protein in esophageal squamous cell carcinoma cells.3.A C57BL6 mouse subcutaneous xenograft model using m EC2 cells was established.After tumor formation,the mice were divided into anti-NRG1 treatment group,anti-PD-1 treatment group,combination treatment of anti-NRG1 and anti-PD-1 group,then the differences in tumor weight and volume between groups were observed.Results:1.NRG1 is highly expressed in esophageal cancer and is also up-regulated in esophageal squamous cell carcinoma.Patients with high NRG1 expression had a poor prognosis.2.PD-L1 was highly expressed in esophageal cancer and is positively correlated with the expression of NRG1.PD-L1 was highly expressed in esophageal squamous cell carcinoma.In esophageal squamous cell carcinoma,knockdown of NRG1 resulted in the down-regulation of PD-L1 expression and the addition of exogenous recombinant human NRG1 protein resulted in the up-regulation of PD-L1 expression.3.We found that combination therapy using anti-NRG1 and anti-PD-1 had a better therapeutic effect in animal experiments.Conclusion:NRG1 is highly expressed in esophageal squamous cell carcinoma,and promotes tumor immune escape mediated by PD-L1 expression.The combination therapy of anti-NRG1 and anti-PD-1has a better therapeutic effect on esophageal squamous cell carcinoma,providing a theoretical basis for exploring novel therapeutic targets and combined treatment in esophageal squamous cell carcinoma.