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Series GSE249124 Query DataSets for GSE249124
Status Public on Dec 02, 2023
Title Shaping immune landscape of colorectal cancer by cholesterol metabolites [C57BL/6]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC) (Picard et al., 2020). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC. Through secretion of distal cholesterol precursors, which directly activate RORgt, MSS CRC cells can polarize T cells toward Th17 cells that have well-characterized pro-tumor functions in colorectal cancer. Analysis of large human cancer cohorts revealed an asynchronous pattern of the cholesterol biosynthesis in MSS CRC, which is responsible for the abnormal accumulation of distal cholesterol precursors. Inhibiting the cholesterol biosynthesis enzyme Cyp51 by ketoconazole, a clinically approved drug, reduced the levels of intratumoral distal cholesterol precursors and suppressed tumor progression through a Th17-modulation mechanism in preclinical MSS CRC models. Our study therefore reveals a novel immune-modulation mechanism of oncometabolites and an invention strategy for the difficult-to-treat MSS CRC.
Overall design Use AOM/DSS induced CRC model of C57BL/6 mice and take paired tumor and colon tissue to perform RNA-seq.
Web link
Contributor(s) Bai Y, Li T, Wang Q, You W, Wang Z, Zhu Z, Xu C
Citation(s) 38177537
BioProject PRJNA787053
Submission date Dec 01, 2023
Last update date Mar 07, 2024
Contact name Haochen Yang
Organization name Shanghai Institute of Biochemistry and Cell Biology
Lab Chenqi Xu Lab
Street address 320 Yue-yang Road
City Shanghai
State/province Shanghai
ZIP/Postal code 200031
Country China
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM7926999 CAC-T2
GSM7927000 CAC-T4
GSM7927001 CAC-T20

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Supplementary file Size Download File type/resource
GSE249124_RNAseq_CAC_count_FPKM.xlsx 5.3 Mb (ftp)(http) XLSX
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Raw data are available in SRA

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