Expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on human hepatocellular carcinoma

Abstract

Costimulation mediated by costimulatory molecules, such as B7‐1 and B7‐2, which are ligands for the CD28/cytolytic T lymphocyte associated antigen (CTLA)‐4 counter‐receptor, plays an important role in the induction of T cell‐mediated antitumor immunity. We investigated the expressions of B7‐1, B7‐2, and human leukocyte antigen (HLA) class I in seven human hepatocellular carcinoma (HCC) cell lines by reverse transcription‐polymerase chain reaction (RT‐PCR) and flow cytometric analysis. RT‐PCR showed that all these human HCC cell lines were positive for B7‐1 and B7‐2 at the messenger RNA (mRNA) level. Flow cytometric analysis revealed that they all expressed B7‐1, B7‐2, and HLA class I on the cell surface. However, the expression levels of B7‐1 and B7‐2 were very low whereas those of HLA class I were high. B7‐1 and B7‐2 expression could be increased by treatment with interferon α and interferon γ in a dose‐dependent manner, although the expression levels of B7‐1 and B7‐2 after interferon treatment remained low. By transfecting Hep3B cells with a plasmid containing human B7‐1 complementary cDNA (cDNA), we were able to establish Hep3B cell lines strongly expressing B7‐1. From mixed lymphocytes and tumor cultures analysis, the primary cytolytic activity against parental Hep3B cells could be induced effectively by B71‐transfected Hep3B cells. These findings suggested that B7‐1 gene transfer is the best way to induce strong expression of this molecule and this might be useful for immuno‐gene therapy against human HCC.