The Relationship Between Programmed Death-Ligand 1 and Cancer Stem Cells in Ovarian Cancer: Implications for Immunotherapy

Suci Pratiwi; Arfianti Arfianti; Suyanto Suyanto; Wiwit Ade Fidiawati

doi:10.31557/APJCB.2026.11.4.1181

Authors

Suci Pratiwi Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia.
Arfianti Arfianti Departement of Medical Biology, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia.
Suyanto Suyanto Department of Anatomical Pathology, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia.
Wiwit Ade Fidiawati Faculty of Medicine, Riau University, Pekanbaru, Indonesia.

DOI:

https://doi.org/10.31557/APJCB.2026.11.4.1181

Keywords:

ovarian cancer; PD-L1; cancer stem cells; immunotherapy; tumor microenvironment

Abstract

Objective: To review the relationship between programmed death-ligand 1 (PD-L1) expression and cancer stem cells (CSCs) in ovarian cancer and to explore their implications for tumor progression, immune evasion, therapeutic resistance, and immunotherapy strategies.

Materials and Methods: A narrative review was conducted using major electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar, focusing on studies investigating PD-L1 expression, CSC biology, tumor microenvironment interactions, and key signaling pathways in ovarian cancer.

Results: Emerging evidence indicates that CSCs play a pivotal role in tumor progression, recurrence, and resistance to conventional therapies in ovarian cancer. PD-L1 has been suggested to contribute not only to immune suppression but also to the maintenance of stem-like properties through activation of multiple signaling pathways, including Notch signaling and epithelial mesenchymal transition-related mechanisms. Components of the tumor microenvironment, particularly myeloid-derived suppressor cells, further enhance CSC phenotypes and PD-L1 expression via cytokine-mediated signaling. Elevated PD-L1 expression in CSC populations may partly explain the limited efficacy of immune checkpoint inhibitors in ovarian cancer, although further clinical validation is still required.

Conclusion: The interplay between PD-L1 and cancer stem cells represents a key mechanism underlying immune evasion, tumor progression, and therapeutic resistance in ovarian cancer. Current evidence suggests that CSC-associated PD-L1 expression is closely linked to stemness maintenance and immunosuppressive tumor microenvironment dynamics. Although most findings are derived from preclinical studies, targeting the PD-L1–CSC axis, particularly in combination with CSC-directed or microenvironment-modulating strategies, may enhance the effectiveness of immunotherapy and improve clinical outcomes.