Cellular senescence in ovarian cancer: context-dependent effects on tumor immunity and therapy response

Cellular senescence is a stress-responsive state marked by sustained proliferative arrest and changes in metabolism, chromatin organization, secretion, and immune signaling. In ovarian cancer (OC), platinum therapy and PARP inhibition can generate senescence-associated states with distinct consequences. Their effects depend on treatment context, cellular compartment, stability of arrest, and the surrounding immune state. Therapy-induced senescent tumor cells may increase antigen presentation and inflammatory signaling and, in immune-competent settings, facilitate dendritic-cell and CD8+ T-cell responses. Persistent senescence can instead maintain a SASP that remodels stromal and immune compartments and may support residual disease, dissemination, or relapse. OC studies have linked altered senescence responses to cisplatin resistance, while senescence-associated states have also been reported after PARP inhibition and taxane treatment. Senescence in CAFs, mesothelial cells, adipose-associated stroma, and immune cells can further alter tumor-cell survival, invasion, immune surveillance, and treatment response. We therefore distinguish stable TIS from reversible senescence-like or dormant states and separate tumor-cell effects from stromal and immune effects. Senolysis, SASP modulation, ferroptosis, and immune-mediated clearance represent potential strategies, but most evidence remains preclinical. Overall, senescence in OC is best viewed as a context-dependent state that can either support antitumor immunity or facilitate immune escape and treatment persistence.