Impact of cancer immunotherapies on oocyte health and ovarian function

The ovary is an immunologically active organ in which tightly regulated interactions between immune cells, cytokines, and reproductive hormones are essential for follicle and oocyte development, ovulation, luteal function, and maintenance of the ovarian reserve. Immune checkpoints such as PD-1, PD-L1, and CTLA-4 are increasingly recognized as key regulators of immune tolerance beyond classical lymphoid tissues, yet their roles within the ovary remain poorly defined. Immune checkpoint inhibitors (ICIs), which target these pathways to enhance anti-tumor immunity, have transformed cancer treatment and are increasingly administered to women of reproductive age. While traditional cancer therapies are well known to compromise ovarian function and fertility, the reproductive consequences of ICIs are only beginning to emerge. Here we synthesize current knowledge of ovarian immune biology, with a focus on T cells and immune checkpoint signaling, and integrate clinical, preclinical, and mechanistic evidence linking immune checkpoint blockade to ovarian dysfunction. We discuss immune-related adverse events (irAEs), their management, and emerging evidence that the ovary may be uniquely sensitive to immune checkpoint perturbation. Collectively, this review highlights emerging knowledge of T cells and immune checkpoints in the ovary, highlights critical gaps in our understanding of immune - ovarian crosstalk, and discusses the urgent need to define the reproductive risks of ICIs to inform fertility preservation strategies and clinical decision-making for women with cancer.