Programmed cell death protein 1 (PD-1) and Fas receptor (CD95) signaling pathways (PD-1/PD-L1 and Fas/FasL axes)

The target description "Host immune effector cells via PD-L1/PD-L2–PD-1 and FasL–Fas axes" refers to two distinct but functionally integrated pathways that govern the activation, exhaustion, and survival of immune cells. The PD-1 axis, involving Programmed cell death protein 1 (PD-1) and its ligands PD-L1 and PD-L2, acts as a critical immune checkpoint that maintains peripheral tolerance and prevents autoimmunity by delivering inhibitory signals to T cells (Pardoll, 2012, Nature Reviews Cancer; UniProt Q15116, Q9NZQ7). Tumors frequently exploit this pathway by overexpressing PD-L1 to induce T-cell exhaustion and evade immune surveillance. The Fas/FasL axis, comprising the Fas receptor (CD95) and Fas ligand (CD178), is a primary mediator of the extrinsic apoptosis pathway, where ligand binding triggers a caspase cascade leading to programmed cell death (Strasser et al., 2009, Immunity; UniProt P25445, P48023). This axis is essential for eliminating infected or malignant cells and for the resolution of immune responses through activation-induced cell death. Therapeutic strategies targeting these pathways, such as the PD-1 inhibitors pembrolizumab and nivolumab, aim to reinvigorate host immune effector cells to combat cancer, while Fas-directed therapies like asunercept are investigated for their ability to modulate cell survival in inflammatory and neoplastic conditions (Sharpe & Pauken, 2018, Nature Reviews Immunology).

Other names

PD-1/PD-L1 axisFas/FasL axisCD279/CD274 axisCD95/CD178 axisProgrammed death signalingExtrinsic apoptosis pathwayImmune checkpoint and death receptor signaling

Blockade of the PD-1/PD-L1 interaction to prevent inhibitory signaling in T cells and restore effector function; modulation of the Fas/FasL interaction to regulate extrinsic apoptosis in target cells or immune cells.