Negatively charged plasma membrane phospholipids

Negatively charged plasma membrane phospholipids, primarily phosphatidylserine (PS), are essential components of the cellular lipid bilayer that are typically sequestered in the inner leaflet of healthy cells by ATP-dependent flippases (Birge et al., 2016). In response to cellular stress, apoptosis, or malignant transformation, these lipids flip to the outer leaflet, where they serve as critical signaling molecules (Thorpe, 2010). In the tumor microenvironment, exposed PS acts as a potent immunosuppressive signal, inhibiting the activity of immune cells and promoting self-tolerance (Soares et al., 2008). Therapeutic strategies involve using monoclonal antibodies or ligand-based molecules to bind these exposed phospholipids, thereby neutralizing their immunosuppressive effects or directing cytotoxic agents to the site (Belzile et al., 2016). This approach is particularly relevant in oncology and virology, where anionic phospholipids facilitate tumor evasion and viral entry, respectively. Drugs like bavituximab target these lipids to convert the immunosuppressive tumor environment into an immunostimulatory one, enhancing the efficacy of other treatments like chemotherapy or checkpoint inhibitors.

Other names

Anionic phospholipidsAcidic phospholipidsPhosphatidylserinePhosphatidic acidPhosphatidylinositol

Binding to externalized anionic phospholipids on the outer leaflet of the plasma membrane to neutralize immunosuppressive signaling, induce antibody-dependent cellular cytotoxicity (ADCC), or inhibit viral entry.