PGE2 effect on unstimulated and exhausted human CD8+ T-cells
Prostaglandin E2 (PGE2) is overexpressed in many tumors and plays an important role in suppressing T-cell function. In this study, we investigated the effect of PGE2 in human T-cells. Importantly, PGE2 caused profound transcriptomic changes both in unstimulated and exhausted T-cells with many genes and pathways altered including T-cell lipid metabolism.  Our study suggests that PGE2-induced metabolic reprogramming is detrimental to dysfunctional T-cells and TIL, and its manipulation could be used to dampen the immunosuppressive effects of PGE2. Overall design: we adapted an in-vitro model of T-cell chronic activation by repetitively stimulating human peripheral blood lymphocytes (PBLs) with anti-CD3/CD28 beads (Dunsford et al., 2020) and low-dose IL2 (60IU). Following 10 days of stimulation, chronically activated T cells or unstimulated T-cells were treated with PGE2 for 24 hours. CD8+ T-cells were then sorted and RNA extracted.