Characterization of a Soluble B7-H3 (sB7-H3) Spliced from the Intron and Analysis of sB7-H3 in the Sera of Patients with Hepatocellular Carcinoma

Abstract

B7-H3 is a recently discovered member of the B7 superfamily molecules and has been found to play a negative role in T cell responses. In this study, we identified a new B7-H3 isoform that is produced by alternative splicing from the forth intron of B7-H3 and encodes the sB7-H3 protein. Protein sequence analysis showed that sB7-H3 contains an additional four amino acids, encoded by the intron sequence, at the C-terminus compared to the ectodomain of 2Ig-B7-H3. We further found that this spliced sB7-H3 plays a negative regulatory role in T cell responses and serum sB7-H3 is higher in patients with hepatocellular carcinoma (HCC) than in healthy donors. Furthermore, we found that the expression of the spliced sb7-h3 gene is higher in carcinoma and peritumor tissues than in PBMCs of both healthy controls and patients, indicating that the high level of serum sB7-H3 in patients with HCC is caused by the increased expression of this newly discovered spliced sB7-H3 isoform in carcinoma and peritumor tissues.