The Role of Senescence, its Therapeutic Relevance and Clinical Implications in the Tumor Microenvironment.

Cellular senescence is characterized by cell cycle arrest, resistance to apoptosis, the expression of senescence markers, and the acquisition of senescence-associated secretory phenotype (SASP). In this review, we discuss the role of cellular senescence within the tumor microenvironment. Some senescent innate immune cells fail to sustain their antitumor function and may even promote tumor progression. Senescent CD8⁺ and CD4⁺ T cells become dysfunctional and are implicated in immunosuppression, angiogenesis, and resistance to immunotherapy. Research on stromal senescence primarily focuses on the SASP. The SASP functions as a double-edged sword. It promotes immune surveillance in the early stages of a tumor while inhibiting tumor immunity in its advanced stages. Strategies to target senescence in cancer therapies include four main approaches: inducing senescence, inhibiting tumor-promoting SASP, clearing senescent cells, and reversing senescence. Although not yet in clinical practice, these approaches hold promise for future cancer treatments.