Duygu Kırkık, Furkan Aydın, Sevgi Kalkanlı Taş
Turkish Journal of Immunology - 2025;13(3):122-131
Circular RNAs (circRNAs) have gained attention in cancer immunotherapy, particularly in the context of immune checkpoint blockade therapies targeting programmed cell death 1 (PD-1). In this review, we aimed to elucidate the complex interactions between circRNAs and the PD-1 axis across various malignancies, highlighting their pivotal roles in modulating tumor immunity and influencing therapeutic responses in in vitro, in vivo, and in clinical studies. Beginning with an overview of circRNA biogenesis and functionalities, we examine circRNA-mediated mechanisms that impact the PD-1 pathway in cancers such as colorectal, gastric, pancreatic, hepatocellular, bladder, breast, lung, and metastatic melanoma. CircRNAs exhibit diverse functions, including acting as microRNA (miRNA) and protein sponges, translational modulators, and gene expression regulators, thereby intricately modulating the efficacy of PD-1 blockade therapy. Despite remarkable advancements, the field necessitates further investigation to unravel the full spectrum of circRNA-PD-1 interactions and translate these findings into clinical practice effectively. Our review underscores the significant translational potential of circRNAs in cancer immunotherapy, highlighting their multifaceted role in shaping innovative therapeutic strategies. These circRNAs offer insights into the molecular mechanisms of malignancies and hold promise as reliable biomarkers for early detection, prognosis, and monitoring of treatment responses. By integrating circRNA profiling into clinical practice, we envision the development of more personalized treatment approaches that cater to the unique molecular and immune landscapes of individual patients, ultimately revolutionizing cancer management and improving patient outcomes.
