Senescence-associated antigens (SAA)

Senescence-associated antigens (SAAs) are a diverse group of cell surface proteins and MHC-presented peptides that are specifically or preferentially expressed by cells in a state of cellular senescence (Amor et al., 2020). In oncology, these antigens are found on senescent tumor cells and senescent stromal cells, such as cancer-associated fibroblasts, which often accumulate following chemotherapy or radiotherapy in a process known as therapy-induced senescence (Marin et al., 2023). Key examples of these antigens include the urokinase-type plasminogen activator receptor (uPAR), glycoprotein non-metastatic melanoma protein B (GPNMB), and dipeptidyl peptidase 4 (DPP4) (Yoshida et al., 2021). While senescent cells are non-proliferative, they remain metabolically active and secrete a pro-tumorigenic cocktail of factors known as the senescence-associated secretory phenotype (SASP), which promotes chronic inflammation, immunosuppression, and therapy resistance (Prieto et al., 2023). Therapeutic strategies targeting SAAs, such as CAR-T cells and therapeutic vaccines, aim to selectively eliminate these harmful populations to restore tissue homeostasis and enhance the efficacy of conventional cancer treatments. However, the clinical application of SAA-targeted therapies must carefully manage potential toxicities related to the disruption of beneficial senescent cells involved in physiological processes like wound healing and tissue repair (Amor et al., 2024).

Other names

Tumor-associated antigens from senescent tumor cellsSeno-antigensSenescence-associated surface proteinsSenescence-specific antigensSASP surface proteins

Selective immune-mediated clearance of senescent cells (senolysis) via recognition of surface-expressed antigens by CAR-T cells, monoclonal antibodies, or vaccine-induced cytotoxic T cells.