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GEO help: Mouse over screen elements for information. |
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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
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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.
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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.
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Contributor(s) |
Liu X, Kong Y, Li C, Liu J, Wu S |
Citation missing |
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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
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Street address |
1881 East Rd
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City |
Houston |
State/province |
TX |
ZIP/Postal code |
77054 |
Country |
USA |
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Platforms (2) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (6)
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Relations |
BioProject |
PRJNA1103932 |
Supplementary file |
Size |
Download |
File type/resource |
GSE264739_RAW.tar |
711.4 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
Raw data are available in SRA |
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