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

Abstract

The interaction of B7H1 in tumor cells with programmed death-1 (PD-1) in Tcells plays an important role in the suppression of immune responses. However, the effects of the expression of B7H1 and the PD-1/programmed death1 ligand1 (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 2human 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 invitro. 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.