Phosphatidylserine-mediated phagocytosis

Phosphatidylserine-mediated phagocytosis, commonly referred to as efferocytosis, is a fundamental biological process responsible for the silent and non-inflammatory removal of apoptotic cells. Under physiological conditions, phosphatidylserine (PS) is restricted to the inner leaflet of the plasma membrane, but it is externalized to the outer leaflet during apoptosis, acting as a universal "eat-me" signal for phagocytes. This signal is recognized by a variety of receptors, including the TAM family (Tyro3, Axl, MerTK) and TIM family (TIM-1, TIM-4), often mediated by bridging opsonins like Gas6 and Protein S. In the context of cancer, the persistent exposure of PS in the tumor microenvironment creates an immunosuppressive milieu that facilitates tumor growth and evasion of the immune system. Therapeutic interventions targeting this pathway include antibodies that mask PS to stimulate an immune response and small molecule inhibitors of PS receptors to block efferocytosis-mediated immunosuppression. Conversely, defects in this pathway are linked to autoimmune diseases and atherosclerosis, making the enhancement of PS-mediated clearance a potential therapeutic strategy for chronic inflammatory conditions.

Other names

EfferocytosisApoptotic cell clearancePhosphatidylserine-mediated engulfmentProgrammed cell removalPS-mediated phagocytosis

Blocking the immunosuppressive phosphatidylserine signal or inhibiting its receptors (TAM family) to enhance anti-tumor immunity; or enhancing the pathway to treat inflammatory diseases.