C-Myc regulates PD-L1 expression in esophageal squamous cell carcinoma.

Immunotherapy using antibodies blocking the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway has achieved great success in preclinical models and the clinical treatment of esophageal squamous cell carcinoma (ESCC). The c-Myc proto-oncogene helps prevent immune cells from attacking tumor cells by inducing PD-L1 expression. However, the underlying mechanisms of c-Myc and PD-L1 in ESCC remain unclear, and a thorough understanding of this regulation would allow the development of new approaches to enhance antitumor immunity. In the present study, the positive relationship between c-Myc and PD-L1 was explored in the Cancer Genome Atlas dataset using the bioinformatics tool GEPIA, and was confirmed in 105 ESCC tissues by immunostaining (r=0.516, P<0.001). The patients positive for both proteins had a poorer overall survival (P=0.032). Furthermore, in ESCC cell lines, c-Myc overexpression, depletion, and inhibition was able to regulate the expression of PD-L1. Also, the ChIP assays showed that the increase in PD-L1 expression was likely due to the binding of c-Myc to the PD-L1 promoter. Taken together, c-Myc and PD-L1 levels were significantly correlated, and c-Myc expression regulated the expression of PD-L1 in ESCC cells. In addition, a small molecule inhibitor of c-Myc effectively regulated PD-L1 expression. This indicates that synergistic therapy combining a c-Myc inhibitor with PD-L1 immunotherapy might be a promising new treatment strategy for ESCC.

[Comparison of thoracoscopic esophagectomy in decubitus position with prone position].

OBJECTIVE: To compare the safety and efficacy between two different surgical approaches for thoracoscopic esophagectomy including left lateral decubitus position and prone position. METHODS: From January 2008 to December 2009, 88 patients who underwent thoracoscopic esophagectomy were enrolled in this study. Among them, 52 patients were placed in decubitus position and 36 patients were placed in prone position. RESULTS: No conversion to thoracotomy occurred in either group. The operative time was shorter in the prone group than that in the decubitus group (70 ± 20 min vs. 82 ± 17 min, P<0.01). Blood loss during operation was less in the prone group(100 ± 52 ml vs. 139 ± 54 ml, P<0.01). More lymph nodes were harvested from chest in the prone group(12.2 ± 6.2 vs. 8.6 ± 4.3, P<0.01). There was no significant difference between the two groups in morbidity. CONCLUSION: Thoracoscopic esophagectomy in prone position is associated with better exposure of surgical filed, shorter operative time, less blood loss, and more extensive lymph node dissection as compared to decubitus position.