The effects of ATP and CD39 inhibition in monocyte-derived dendritic cells.
Extracellular ATP (eATP) is a damage associated molecular pattern (DAMP) that may be released by cancer cells as a result of chemotherapy-induced immunogenic cell death (ICD). We have demonstrated that preserving extracellular ATP (eATP) by inhibiting the extracellular ATPase CD39 boosts anti-tumor immunity in various models. We recently reported the development of AB598, a very specific and potent therapeutic antibody that inhibits CD39 enzymatic activity. We demonstrated using a cancer cell-moDC co-culture system that chemotherapy-induced ATP release with AB598 inhibition is sufficient to activate moDCs to a greater antigen presenting cell (APC) phenotype. Using this co-culture system, we generated and tested an ATP signature that shows promising utility in tumor biopsies. Overall design: RNAseq of monocyte-derived dendritic cells (moDCs) in various co-culture conditions including combinations of A549 cells, docetaxel, AB598 or isotype control, or ATP. Viable moDCs were sorted out from A549 cells using positive selection for CD11c.