Lujun Chen, Changping Wu, Jingting Jiang

Department of Tumor Biological Treatment, Third Affiliated Hospital of Soochow University

Objective:B7-H3, a member from B7-family co-stimulatory ligands, plays an important role in adaptive immune responses. In addition, recent studies also demonstrated that B7-H3 could be highly expressed in various types of human cancers, and its expression level was significantly associated with cancer patients' clinicopathological parameters and postoperative prognoses. As of know, the exact role of B7-H3 expression in human esophageal cancer still remains elusive. Method: In the present study, we characterized the B7-H3 expression in the human esophageal cancer cell line Eca-109 and TE-1, and in 174 cases of human esophageal cancer tissues, and to analyze its clinical implications and its correlation to T cell infiltration. By using the RNA interference technology to down-regulate the B7-H3 expression in human esophageal cancer cell line Eca-109, we further studied the contribution of high B7-H3 expression to the biological features of this malignancy. Result: Our results showed that B7-H3 was highly expressed in the cell line Eca-109 and TE-1, the high expression level of B7-H3 in esophageal cancer tissues was significantly associated with tumor invasion and patient's poor survival. Moreover, the higher B7-H3 expression was significantly and inversely correlated to the CD3⁺T cells infiltration in tumor nest of the cancer tissues. We constructed the recombinant lentivirus of siRNA targeting B7-H3, and the cellular studies showed that the down regulation of B7-H3 expression could suppress the proliferation, colony formation ability, migration and invasion in Eca-109 cells, which was consistent with the finding from the clinical sample cohort study. Conclusion: Collectively, the high B7-H3 expression was involved in the cancer progression of human esophageal cancer, and might contributed to the negative regulation of T-cell mediated antitumor response in tumor microenvironment, and the proliferation and mobility of esophageal cancer cells. The detailed mechanism and the potential value of clinical use targeting B7-H3 against human esophageal cancer merit further investigation.

Key Words: B7-H3  esophageal cancer  prognosis