A cycle involving HMGB1, IFN-γ and dendritic cells plays a putative role in anti-tumor immunity

Abstract

An important subset in regulating antitumor immunity is the maturation and accumulation of intratumor dendritic cells (DCs), inducing potent T cell cytotoxicity. In this study, we explored how the soluble abundant high-mobility group box 1 protein (HMGB1) affected DC activation and retention within lung cancers, and in which way the resultant interferon-γ (IFN-γ) further enhanced DC maturation and accumulation. It was discovered that HMGB1 was correlated with DC markers HLA-DR and CD86 in lung cancers at both mRNA and protein level. Further analyses showed HMGB1 enhanced the maturation of DCs, indicated by upregulated IFN-γ in CD8⁺ T cells. Additionally, HMGB1 increased the accumulation of DCs by promoting CCR5 and CXCR3 production. Moreover, the resultant IFN-γ elevated the levels of HMGB1 and DC-associated chemokines, CCL5, CXCL10 and CXCL11 in tumor cells. Hence, the HMGB1-IFN-γ cycle may represent an important mechanism underlying DC-mediated anti-tumor immune response.

Keywords: CCL5; CCR5; CXCL10; CXCL11; CXCR3; Cytotoxic T lymphocyte; Dendritic cell; High-mobility group box 1; Interferon-γ.