Cellular senescence in cancer immunology and potential therapeutic strategy

Cellular senescence represents a state of stable, often irreversible cell cycle arrest. Unlike apoptosis, senescent cells (SCs) remain metabolically active and engage in robust secretory activity, most notably through the senescence-associated secretory phenotype (SASP). The SASP exerts profound and context-dependent effects on tumor initiation and progression. This review analyzes the dual role of senescent cells in tumor immunity. On one hand, they can exhibit anti-tumorigenic effects through SASP-mediated enhancement of immune surveillance and their inherent high immunogenicity. On the other hand, they can promote tumorigenesis by fostering an immunosuppressive microenvironment, polarizing immune cells via the SASP, and upregulating senescence-associated immune checkpoints (SAICs) to facilitate immune escape. These dual characteristics inform promising therapeutic strategies: first, inducing senescence in tumor cells, and second, selectively eliminating the resulting senescent populations. Notably, systemic senescence induction can cause off-target effects in healthy tissues, underscoring the need for targeted delivery systems. In conclusion, we highlight emerging senescence-targeted immunotherapies as a next-generation approach to strategically harness senescence for cancer control.