CD80 transfected human hepatocellular carcinoma cells activate cytotoxic T lymphocytes to target HCC cells with shared tumor antigens

Abstract

Abstract. Human HCC cell lines (BEL-7402, SMMC-7721 and QGY-7703) do not express CD80 molecules, although they express MHC class I molecules and ICAM-1. HCC's poor immunogenicity may therefore be due to lack of CD80 molecules. This study first investigated whether CD80 molecules could provide minimal co-stimulatory signal for establishing an efficient anti-tumor immunity in HCC and second, whether the transfection of CD80 into the BEL-7402 cell line could induce T cell activation for targeting other HCC cell lines expressing shared common antigens. The transfection of cDNA encoding CD80 into ICAM-1 + HCC BEL-7402 cells was confirmed by flow cytometrical analysis. The CD80-tranfected cells could enhance the immunogenicity of BEL-7402 cells as detected by T cell proliferation assay, and also activated the T cells at a higher proliferation rate comparing with the BEL-7402 cells transfected with vector only. The CD80-transfected cell line was also found able to activate T cells which subsequently induced cell lysis of SMMC-7721, QGY-7703 and parent BEL-7402 cell lines as detected by cytotoxicity assay. It can be concluded that the cytotoxicity was due to MHC class I restricted CD8 + cytotoxic T lymphocytes, but not natural killer (NK) cells, since this cytotoxic effect could be blocked by anti-MHC class I antibody and the cytotoxicity was shown very low in NKcell-sensitive K562 cell line. Electroporation of CD80 cDNA into human HCC cells could increase the expression of the functional CD80 molecules and enhance the immunogenicity of the genetically-modified HCC cells to activate T cells for targeting 3 HCC cell lines in an HLA-restricted manner.

Engaging stimulatory immune checkpoint interactions in the tumour immune microenvironment of primary liver cancers – how to push the gas after having released the brake

“…In the TIME multiple cell types can deliver CD28 stimulatory signals as CD80 and CD86 are expressed on intra-tumoural B cell, BDCA1 + myeloid DC (mDC), and CD14 + monocytes in both HCC and CCA ( 18 ). HCC tumour cells themselves, however, have demonstrated relatively low B7 family member expression ( 41 , 42 ).…”

Modulation of Tumor Immunity by Soluble and Membrane-Bound Molecules at the Immunological Synapse

“…These tumors have been shown to express T cell inhibitory molecules such as B7-H1 and ICOSL to engage their inhibitory counterparts on the T cell surface (Figure 2(a)). On the contrary, tumors that are induced to express costimulatory molecules that activate T cells, such as B7.1 (also known as CD80), and B7.2 (also known as CD86) are cleared by the immune system and thus may be used as a strategy to promote tumor immunity [148, 149]. …”