Abstract

PLK1 (Polo-like kinase 1) plays a critical role in the progression of lung adenocarcinoma (LUAD). Recent studies have unveiled that targeting PLK1 improves the efficacy of immuno- therapy, highlighting its important role in the regulation of tumor immunity. Nevertheless, our understanding of the intricate interplay between PLK1 and the tumor microenvironment (TME) remains incomplete. Here, using genetically engineered mouse model and single- cell RNA-seq analysis, we report that PLK1 promotes an immunosuppressive TME in LUAD, characterized with enhanced M2 polarization of tumor associated macrophages (TAM) and dampened antigen presentation process. Mechanistically, elevated PLK1 coin- cides with increased secretion of CXCL2 cytokine, which promotes M2 polarization of TAM and diminishes expression of class II major histocompatibility complex (MHC-II) in profes- sional antigen-presenting cells. Furthermore, PLK1 negatively regulates MHC-II expression in cancer cells, which has been shown to be associated with compromised tumor immunity and unfavorable patient outcomes. Taken together, our results reveal PLK1 as a novel mod- ulator of TME in LUAD and provide possible therapeutic interventions.

Document Type

Article

Publication Date

6-2024

Notes/Citation Information

© 2024 Kong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Digital Object Identifier (DOI)

https://doi.org/10.1371/journal.pgen.1011309

Funding Information

This study is supported by NIH R01 CA157429 (XL, YK, MZ), R01 CA196634 (XL, QZ, YZ), R01 CA264652 (XL, CL, FM, SW, CW), R01CA256893 (XL, XW, CW). This study is also supported by the Biospecimen Procurement & Translational Pathology, Biostatistics and Bioinformatics, Redox Metabolism, Flow Cytometry and Immune Monitoring Shared Resources, and OncoGenomics Shared Resource Facility of the University of Kentucky Markey Cancer Center (P30CA177558) to JL, DBA, CW, XL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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