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 immunotherapy, 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 coincides with increased secretion of CXCL2 cytokine, which promotes M2 polarization of TAM and diminishes expression of class II major histocompatibility complex (MHC-II) in professional 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 modulator of TME in LUAD and provide possible therapeutic interventions.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Conflict of Interest: The authors declare no conflict of interest.
The latest version of our manuscript has mainly fixed the inconsistency of our scRNA-seq analysis among multiple figures. Besides, some typos and errors have also been corrected. This version is ready for peer review.
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE206644
Data availability
All data are included in this article. Bulky RNA-seq data was deposited in GEO under accession number GSE206644.