Downlo le preclinical modeling currently exists to support the use of OX40 agonists as therapeutic agents in tting of advanced cancers, as well as the mechanisms through which therapeutic efficacy is achieved. ow that treatment of mice bearing well-established day 17 sarcomas with a novel OX40 ligand–Fc protein (OX40L-Fc) resulted in tumor regression or dormancy in the majority of treated anima...

Background and aims: Tumor necrosis factor (TNF) is one of the inflammatory cytokines which has an important role in inflammation and migration of other inflammatory cells to the atherosclerotic plaques. OX40L is a member of the TNF super family receptor protein. OX40 and OX40 ligand are co-stimulators for T-cells and can increase inflammatory response in atherosclerotic plaques. The aim of thi...

Oxidative low-density lipoprotein (Ox-LDL) is a key risk factor for the development of atherosclerosis, and it can stimulate the expression of a variety of inflammatory signals. As a new and highly sensitive inflammation index, OX40L may be a key to understanding the mechanisms that regulate interactions between cells within the vessel wall and inflammatory mediators during the development of a...

Ox40 ligand (Ox40L) locus genetic variants are associated with the risk for systemic lupus erythematosus (SLE); however, it is unclear how Ox40L contributes to SLE pathogenesis. In this study, we evaluated the contribution of Ox40L and its cognate receptor, Ox40, using in vivo agonist and antagonist approaches in the NZB × NZW (NZB/W) F1 mouse model of SLE. Ox40 was highly expressed on several ...

The development of effector and memory CD4 cell populations depends upon both T cell receptor (TCR) engagement of peptide/major histocompatibility complex (MHC) class II complexes and ligation of costimulatory molecules with counter receptors on antigen-presenting cells (APCs). We showed previously that sustained interactions with APCs could be crucial for optimal expansion of CD4 cells and for...

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases which degrade extracellular matrix proteins and modulate cell proliferation, migration, differentiation and angiogenesis. MMP-2, a member of the gelatinase subfamily of MMPs, participates in the remodeling and resolution of tissue injury and tumorigenesis. We recently identified an unexpected new role for MMP2 in the modulation ...

CD4 Th differentiation is influenced by costimulatory molecules expressed on conventional dendritic cells (DCs) in regional lymph nodes and results in specific patterns of cytokine production. However, the function of costimulatory molecules on inflammatory (CD11b(+)) DCs in the lung during recall responses is not fully understood, but it is important for development of novel interventions to l...

We recently reported that mast cells stimulated via FcepsilonRI aggregation can enhance T cell activation by a TNF-dependent mechanism. However, the molecular mechanisms responsible for such IgE-, Ag- (Ag-), and mast cell-dependent enhancement of T cell activation remain unknown. In this study we showed that mouse bone marrow-derived cultured mast cells express various costimulatory molecules, ...

Pathways involving the costimulatory molecule OX40 and OX40 ligand (OX40L) enhance tumor rejection. It was presumed that this effect was mediated by changes in DCs and/or T cells. In this issue of the JCI, Zaini et al. report that, in mice, intratumoral injection of DCs genetically modified to express OX40L suppressed the growth of a preexisting melanoma by directly triggering an antitumor NKT ...