Cellular Senescence and Immunosenescence in Melanoma: Insights From the Tumor Microenvironment

Senescent tumor and stromal cells drive a pro-inflammatory and immunosuppressive TME through SASP, while aging immune cells exhibit impaired antigen presentation, reduced cytotoxicity, and increased suppressive subsets. These dual processes form a self-reinforcing cycle of chronic inflammation and immune dysfunction, ultimately undermining the efficacy of ICIs. Targeting senescence, through senolytics, senostatics, or SASP modulators, has shown promise in preclinical models and may restore immune competence in melanoma. However, clinical translation requires further investigation to validate safety and efficacy. Addressing both cellular and immune senescence represents a novel and promising direction to overcome therapeutic resistance and improve melanoma outcomes.