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Single-cell analysis identifies PLK1 as a driver of immunosuppressive tumor microenvironment in LUAD.

Authors :
Kong, Yifan
Li, Chaohao
Liu, Jinpeng
Wu, Sai
Zhang, Min
Allison, Derek B.
Hassan, Faisal
He, Daheng
Wang, Xinyi
Mao, Fengyi
Zhang, Qiongsi
Zhang, Yanquan
Li, Zhiguo
Wang, Chi
Liu, Xiaoqi
Source :
PLoS Genetics; 6/17/2024, Vol. 20 Issue 6, p1-23, 23p
Publication Year :
2024

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. Author summary: Our research has pinpointed a vital protein, PLK1, in the development of lung cancer. Through the use of mouse models simulating the onset of lung cancer and genetic sequencing analysis, we've discovered that high level of PLK1 hinders the immune response, making it challenging for the patient's immune system to effectively eliminate lung cancer. Elevated PLK1 level specifically increases the presence of M2 macrophages, a type of immune cell, which, in turn, prevents the immune system from recognizing and attacking lung cancer cells. We've identified that this immune-suppressing effect is linked to PLK1's role in secreting a specific molecule called CXCL2. This molecule promotes the presence of M2 macrophages and hampers the recognition of cancer cells by decreasing the machinery that presents the cancer cells' signature to the immune system, known as MHC-II. These findings suggest that drugs targeting PLK1 could be a promising strategy for treating lung cancer patients. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15537390
Volume :
20
Issue :
6
Database :
Complementary Index
Journal :
PLoS Genetics
Publication Type :
Academic Journal
Accession number :
177927296
Full Text :
https://doi.org/10.1371/journal.pgen.1011309