Immune Checkpoint Inhibition in Ovarian Cancer

Ovarian cancer remains one of the most lethal gynaecological malignancies, in part owing to late presentation and intrinsic resistance to conventional therapies. Immune checkpoint molecules, notably the programmed cell death-1 (PD-1) receptor and its ligand PD-L1, are pivotal in downregulating cytotoxic T-cell activity and permitting tumour immune evasion. Inhibitory pathways such as CTLA-4 and emerging axes like CD24–Siglec-10 further contribute to an immunosuppressive tumour microenvironment. Checkpoint blockade has revolutionised treatment in melanoma and lung cancer, but monotherapy in ovarian cancer has thus far yielded modest response rates. The complexity of the ovarian tumour microenvironment—characterised by dense stroma, heterogeneous antigen presentation and immunosuppressive cell populations—underlies variable patient outcomes. Research is therefore focusing on identifying predictive biomarkers, optimising combination regimens with chemotherapy, targeted agents or other immunotherapies, and understanding resistance mechanisms. Translational studies suggest that patient selection based on PD-L1 expression, tumour-infiltrating lymphocyte density and emerging markers such as CD24 may refine clinical benefit and guide personalised therapeutic strategies.

Research from Nature Portfolio

Recent analysis of paired primary epithelial ovarian carcinomas and their peritoneal metastases has revealed significant discordance in tumour cell PD-L1 expression. Over one-third of cases showed altered PD-L1 status between sites, and higher expression in metastatic deposits correlated with adverse features, including elevated proliferative index and higher histological grade. This work underscores the need to assess metastatic lesions when considering PD-L1 as a predictive biomarker for immune checkpoint therapies and suggests that sampling only the primary tumour may misrepresent therapeutic potential.

Immune Checkpoint Inhibition in Ovarian Cancer publication trend

The graph below shows the total number of articles in immune checkpoint inhibition in ovarian cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Immune checkpoint: Regulatory pathway that modulates T-cell activation and maintains self-tolerance.

PD-1 (Programmed cell death-1): Inhibitory receptor on activated T lymphocytes that limits antitumour responses when engaged.

PD-L1 (Programmed death-ligand 1): Cell-surface ligand expressed by tumour and immune cells that binds PD-1 to suppress T-cell function.

Tumour microenvironment: Complex milieu of cancer cells, stromal elements and immune infiltrates influencing tumour progression.

CD24: Glycosylphosphatidylinositol-anchored surface protein that interacts with Siglec-10 to mediate immune evasion.

Siglec-10: Sialic acid-binding lectin on macrophages that transmits inhibitory signals upon ligand binding.

References

1. The biological roles of CD24 in ovarian cancer: old story, but new tales. Frontiers in Immunology (2023).
2. Differential expression of PD-L1 between primary and metastatic epithelial ovarian cancer and its clinico-pathological correlation. Scientific Reports (2021).
3. Focus on PD-1/PD-L1 as a Therapeutic Target in Ovarian Cancer. International Journal of Molecular Sciences (2022).
4. PD-L1 is highly expressed in ovarian cancer and associated with cancer stem cells populations expressing CD44 and other stem cell markers. BMC Cancer (2023).