Phosphatidylserine receptors (PSR) (PSR)

Phosphatidylserine (PS) is a phospholipid typically sequestered in the inner leaflet of the plasma membrane by flippases, but it becomes externalized on the surface of tumor cells, tumor-associated vascular endothelial cells, and apoptotic cells due to oxidative stress and calcium-dependent scramblase activity (Birge et al., 2016). This externalized PS acts as a "global immunosuppressive signal" in the tumor microenvironment by binding to a variety of phosphatidylserine receptors (PSRs), including the TIM (T-cell immunoglobulin and mucin domain) and TAM (Tyro3, Axl, MerTK) families, as well as CD300a and Stabilin-2 (Huang et al., 2005). These receptors and their associated membrane entry machinery—such as the endocytic pathways and fusogenic proteins like Saposin C—are exploited by tumors to promote an anti-inflammatory environment, facilitate efferocytosis-mediated immune evasion, and even allow viral entry through a process known as apoptotic mimicry (Amara & Mercer, 2015). Therapeutic agents like Bavituximab (a PS-targeting antibody) and BXQ-350 (a SapC-DOPS nanovesicle) target this system to either block immunosuppressive signaling or deliver cytotoxic payloads directly to tumor cells (Davis et al., 2020). By disrupting the PS-PSR axis, these therapies aim to convert the "cold" tumor microenvironment into an immunologically "hot" one, enhancing the efficacy of immune checkpoint inhibitors and other standard-of-care treatments (Belzile et al., 2018).

Other names

PtdSer receptorsPhosphatidylserine-binding receptorsTAM receptorsTIM receptorsApoptotic cell receptorsPhosphatidylserine-targeting system

Blockade of phosphatidylserine-mediated immunosuppressive signaling and inhibition of receptor-mediated endocytosis or membrane fusion in the tumor microenvironment.