Phosphatidylserine (PS) (PS)

Phosphatidylserine (PS) is an anionic phospholipid typically sequestered in the inner leaflet of the plasma membrane of healthy cells [1, 11]. In response to the stressful conditions of the tumor microenvironment, such as hypoxia and oxidative stress, PS is constitutively externalized on the surface of cancer cells and tumor-associated vascular endothelial cells [2, 7]. This externalized PS serves as a potent immunosuppressive signal that engages receptors on immune cells, including TAM and TIM receptors, to inhibit anti-tumor immune responses [5, 10]. By mimicking the "eat-me" signal of apoptotic cells, tumor-externalized PS promotes the polarization of macrophages toward a pro-tumor M2 phenotype and suppresses T-cell activation [12, 14]. Therapeutic agents like bavituximab and SapC-DOPS target this exposed PS to block immunosuppression and enhance the efficacy of other immunotherapies or deliver cytotoxic agents directly to the tumor [6, 9]. Because PS exposure is a common feature of many solid tumors and is further increased by standard treatments like radiation and chemotherapy, it is a promising target for broad-spectrum cancer therapy [1, 13].

Other names

Externalized phosphatidylserineSurface-exposed phosphatidylserineePSAnionic phospholipidEat-me signalTumor-externalized phosphatidylserine

Binding to externalized phosphatidylserine to block immunosuppressive signaling through TAM and TIM receptors, thereby reprogramming the tumor microenvironment from an anti-inflammatory (M2) to a pro-inflammatory (M1) state and enhancing anti-tumor immunity.