Immune evasion of senescent cells: Mechanisms, pathological significance, and targeted interventions
TL;DR
This review summarizes current evidence suggesting that senescent cells persistence is attributable not only to immune system decline but also to active, cell-intrinsic mechanisms of immune evasion and highlights emerging therapeutic strategies aimed at targeting the immune evasion of senescent cells.
Abstract
Cellular senescence is a stress-induced cell-cycle arrest program accompanied by the senescence-associated secretory phenotype (SASP). While senescent cells are typically eliminated through immune surveillance under normal physiological conditions, they tend to accumulate progressively during aging and in chronic diseases. This review summarizes current evidence suggesting that such persistence is attributable not only to immune system decline but also to active, cell-intrinsic mechanisms of immune evasion. We discuss how senescent cells escape clearance by weakening immune recognition, suppressing phagocytic removal, resisting apoptosis, remodeling the inflammatory and structural microenvironment through SASP, and activating inhibitory checkpoint pathways in aged tissues. Furthermore, we investigate the contribution of these mechanisms to representative age-related diseases across multiple organs. Finally, we highlight emerging therapeutic strategies aimed at targeting the immune evasion of senescent cells, including checkpoint modulation, chimeric antigen receptor (CAR)-based cell therapies, vaccination approaches, and other immune-bypass strategies. Collectively, these insights underscore immune evasion as a critical determinant of senescent cell persistence and a promising target for interventions in aging and age-related diseases.