Prostaglandin E receptor 4 (EP4) can suppress innate and adaptive immune responses and promote tumor progression. Inhibition of EP4 can decrease immunosuppressive immune cells and promote innate and adaptive immune responses.
- EP4 is a prostanoid receptor expressed by myeloid-derived suppressor cells (MDSCs),
tumor-associatedmacrophages (TAMs), dendritic cells (DCs), CD8+ effector T cells, natural killer (NK) cells, and other immune cells1-6
- EP4 is a G-protein coupled receptor that suppresses both innate and adaptive immune functions3,4,7
- When EP4 engages its ligand, prostaglandin E2 (PGE2), subsequent signal transduction leads to increased infiltration of immunosuppressive cells (eg, MDSCs and TAMs) and suppression of immune effector cells (eg, CD8+ T cells and NK cells)7
- PGE2-EP4 interactions have been implicated in promoting regulatory T cell (Treg) development7
- Preclinical evidence suggests that blocking PGE2 signaling through EP4 receptors leads to decreased MDSCs/TAMs numbers and increased cytotoxic T- and NK-cell activity1-4
- Research suggests that dual blockade of EP4 and other checkpoint pathways can enhance
T-cellactivity within the tumor microenvironment10
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