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Series GSE264739 Query DataSets for GSE264739
Status Public on May 28, 2024
Title Single-cell analysis identifies PLK1 as a driver of immunosuppressive tumor microenvironment in LUAD
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
 
Overall design 8-week-old LSL-KrasG12D/Trp53fl/fl (KP) and LSL-KrasG12D/Trp53fl/fl/ Rosa26LSL-Plk1 (KPP) mice (n = 3 each group) were intratracheally instilled with adenovirus-expressing Cre recombinase at a viral titer of 2.5 × 10^7PFU per mouse to induce lung cancer. Mice were sacrificed after 12 weeks of adenovirus delivery. Single cell suspensions of tumor tissues were prepared following 10x Genomics Cell Preparation Guide.
 
Contributor(s) Liu X, Kong Y, Li C, Liu J, Wu S
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Submission date Apr 23, 2024
Last update date May 29, 2024
Contact name Chaohao Li
Organization name MD Anderson Cancer Center
Street address 1881 East Rd
City Houston
State/province TX
ZIP/Postal code 77054
Country USA
 
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (6)
GSM8226902 KP, replicate 1, scRNA-seq
GSM8226903 KP, replicate 2, scRNA-seq
GSM8226904 KP, replicate 3, scRNA-seq
Relations
BioProject PRJNA1103932

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Supplementary file Size Download File type/resource
GSE264739_RAW.tar 711.4 Mb (http)(custom) TAR (of MTX, TSV)
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Raw data are available in SRA

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