Rewiring immune cell death in ovarian cancer: pyroptosis, apoptosis, and the immunosuppressive microenvironment

Ovarian cancer remains the most lethal gynecological malignancy, in large part because of its highly immunosuppressive tumor microenvironment (TME) and limited responsiveness to current immunotherapies. Emerging evidence indicates that programmed cell death of immune cells is an important determinant of immune dysfunction, tumor immune escape, and therapeutic resistance. Among these processes, apoptosis and pyroptosis exert distinct but interconnected effects on antitumor immunity. Excessive apoptosis contributes to the depletion of cytotoxic T cells and natural killer (NK) cells, whereas apoptosis-resistant tumor-associated macrophages (TAMs) and other immunosuppressive populations can persist and sustain immune suppression. In contrast, pyroptosis is highly context dependent: controlled activation may enhance antitumor immunity through gasdermin-mediated membrane permeabilization, inflammatory cytokine release, dendritic cell (DC) activation, and improved antigen presentation, whereas excessive or persistent pyroptotic signaling may promote chronic inflammation and recruitment of immunosuppressive myeloid cells. Importantly, apoptosis and pyroptosis are interconnected through shared regulatory nodes, including caspase-8, gasdermin proteins, mitochondrial stress, and inflammatory signaling pathways. This review summarizes the characteristics, key signaling pathways, and functional consequences of pyroptosis and apoptosis in major immune-cell populations within the ovarian cancer microenvironment, with particular emphasis on their context-dependent roles in tumor immune evasion and on opportunities to overcome immunosuppression and improve immunotherapy.