Synthetic small peptides acting on B7H1 enhance apoptosis in pancreatic cancer cells.

The interaction of B7H1 in tumor cells with programmed death-1 (PD-1) in T cells plays an important role in the suppression of immune responses. However, the effects of the expression of B7H1 and the PD-1/programmed death 1 ligand 1 (PD-L1) complex on tumor cells themselves remain largely unknown. In order to clarify this, we induced apoptosis in a number of human pancreatic cancer cells with different expression levels of B7H1 and designed small peptides to interfere with the function of B7H1. In this study, we chose 2 human pancreatic cancer cell lines (BxPC-3 and Panc-1 cells). Cells with a high expression of B7H1 (BxPC-3 cells and Panc-1 cells treated with interferon-γ) presented much lower levels of drug-induced apoptosis after they were incubated with PD-1 immunoglobulin. Furthermore, the percentage of BxPC-3 apoptotic cells transfected with B7H1 siRNA was higher compared to that of cells transfected with control siRNA. Both of these results indicate that the PD-1/PD-L1 complex transfers a reverse signal to B7H1+ pancreatic cancer cells upon drug-induced apoptosis in vitro. This effect may be a substantial factor for drug resistance during antitumor therapies. However, synthetic small peptides designed according to the amino acid residues of the PD-1/PD-L1 complex interrupt this effect successfully by their binding to cell membranes and acting like a blocking agent. This result may lead to a breakthrough in pancreatic cancer treatment.