Anti-CD80 monoclonal antibody, clone 2H20

Toxicity of immunosuppression, notably the risk of infection, increases with age. However, the dynamic changes in innate immune response following transplantation are unclear. Based on recent observations, we hypothesized that pro-inflammatory capacity would decrease with age. We analyzed approximately 300 PBMC samples collected longitudinally in 45 de novo, adult kidney recipients and performed detailed phenotypic and functional profiling of monocytes and T cell subsets. Inflammatory response to TLR4 stimulation and indirect allostimulation using mismatched HLA peptides were assessed. In patients aged >= 56 years, TNF-alpha production by intermediate monocytes was similar to that in younger patients early posttransplant, but diminished substantially later. Adjusted analyses suggested that this was not attributable to confounding factors. In contrast, the alloimmune response to HLA peptides measured by IFN-gamma in CD4(+)T cells and TNF-alpha in monocytes was stable over time, but was low in older recipients. Measurement of CD80-86 surface expression revealed no signal for a lower costimulation capacity of APCs. These results suggest that older recipients have a reduced function of their innate pro-inflammatory immune cells posttransplant while maintaining a stable, low alloimmune response over time. The effect of reduced immunosuppressant doses on preventing this phenomenon needs to be clarified.

One of the main mechanisms for avoiding immune response by cancer cells is mediated by inducing an immunosuppressive environment in the tumor following activation of immune checkpoints, i.e. PD-1 or CTLA-4 receptor inhibitors on T lymphocytes. Interaction inhibition between PD-1 or CTLA-4 and their ligands (PD-L1, CD80, and CD85) leads to unblocking of the T-lymphocyte function, and thus destroys cancer cells. Certain intracellular signaling pathways are also involved in the development of tumor cell immunoresistance. Immunosuppressive pathways' activation blocking may increase the immunological anti-tumor control.