The Trifecta of Polo-like Kinases, Cancer, and the Immune System: Emerging Intersections and Therapeutic Insights

Cancer remains one of the most pressing global health challenges, with immunotherapy being a promising treatment option. However, numerous clinical challenges such as recurrence and resistance persist, underscoring the urgent need for a deeper understanding of the mechanisms that influence immune responses in cancer. Polo-like kinases (PLKs), a family of enzymes with five members, PLK1 through PLK5, have been implicated in cancer progression, and their inhibition is being actively explored for cancer management. While past studies of the PLK family are largely confined to their role in the cell cycle and corresponding chromatin dynamics, recent research has unveiled important connections between PLKs and cancer immunity, particularly in relation to critical signaling pathways such as interferon (IFN) signaling, immunogenic cell death (ICD), TGF-β signaling, and FAS/FASL signaling. While much of the research has focused on PLK1, additional members of the PLK family are beginning to attract attention due to their potential implications in cancer immunity. Understanding the intricate role of PLKs in cancer immunity is an emerging field with tremendous potential. This review offers a comprehensive overview of current knowledge connecting the members of the PLK family with cancer immunology and provides considerations for further research to uncover how PLK signaling can be strategically targeted to optimize cancer immunotherapy to enhance clinical responses.