Han Xiao
Wuhan Medical and Health Center for Women and Children, China Coffee
Title: Soluble CD160 enhances antitumor immunity against murine H22 hepatocarcinoma in vivo
Biography
Biography: Han Xiao
Abstract
The glycosylphosphatidylinositol (GPI)-anchored CD160 is a relatively new co-inhibitory molecular and expressed mainly on cytolytic cells such as CD8+ T cells, natural killer (NK) T cells, NK cells and some CD4+ T cells. CD160 on virus-specific CD8+ T cells is up-expressed and generally associated with T cells dysfunction, thus considered as an exhaustion marker. However, CD160 expression on tumor-specific CD8+ T cells and its contribution to tumor-specific CD8+ T cells impairment remains unclear. Here, we try to decipher its regulatory effects on tumor-specific CD8+ T cells function and seek a new target for tumor therapy. CD8+ T cells were separated from splenocytes of tumor-bearing mice and expression of CD160 and HVEM was detected. A eukaryotic expression plasmid (psCD160) was constructed, expressing the extracellular domain of murine CD160 (soluble CD160) which could block the interaction between CD160 and HVEM by binding HVEM. The activity of proliferation and cytolysis and secretion of cytokines by CD8+ T cells were measured after being incubated by soluble CD160 and specific tumor antigen. The treatment effects of psCD160 combined with tumor-vaccine in vivo were observed by H22 hepatocarcinoma mice tumor model. The up-regulated expression of CD160 on CD8+ T cells from tumor-bearing mice was confirmed to be related to cells dysfunction, characterized by lower proliferation and cytotoxicity activity and less cytokine production. Soluble CD160 enhances CD8+ T cells, resulting in increased IFN-γ, IL-2 and TNF-α secretion and cytolysis against target tumor cells in vitro. The administration of soluble CD160 accompanied with tumor-vaccine inhibited tumor growth and prolonged the survival of tumor-bearing mice. Expression of CD160 defined a relatively decreased activity subset of CD8+ T cells and soluble CD160 augments immunological activity and function of tumor-specific CD8+T cells and acquired significant treatment effects against existent tumor cells in vivo.