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Series GSE261146 Query DataSets for GSE261146
Status Public on Aug 09, 2024
Title Cytoplasmic UHRF1 restrains MHC-I-mediated anti-tumor immune response
Organism Mus musculus
Experiment type Other
Summary Immunotherapy has revolutionized the landscape of cancer treatment. However, both primary and acquired resistance to immunotherapy, emerged during the co-evolution of cancer cells and the tumor microenvironment (TME), commonly restrain long-term tumor control. In exploring the oncogenic activity of Ubiquitin-like with PHD and ring finger domains 1 (UHRF1), we unexpectedly discovered that this epigenetic regulator exhibits altered expression and aberrant cytosolic localization in cancerous tissues. Cytoplasmic translocation of UHRF1 is induced by its phosphorylation on a specific serine in response to signals provided by factors present in the TME, such as TGF-, enabling UHRF1 to bind MHC-I and promote its ubiquitination and degradation via the E3 activity of UHRF1. Down-regulation of MHC-I results in suppression of the antigen presentation pathway to establish a non-T cell-inflamed TME favoring tumor growth. Genetic deletion of UHRF1 synergizes with immune checkpoint blockade (ICB) treatment and induces an anti-tumor memory response by evoking low-affinity T cells upon sustained UHRF1 inactivation. Our study unveils a novel function of UHRF1 in cancer immune evasion and provides a potential target to synergize with immunotherapy and overcome immunotherapeutic resistance.
 
Overall design This data contains 2 TCR-seq datasets. 1. For LLC-OVA tumor model, LLC-OVA shNT or shUHRF1 cells were subcutaneously injected into male C57BL/6J mice and subsequently treated with either 30 µg IgG or CTLA4 antibodies on days 7, 10 and 14. Total RNA was extracted from tumor tissues day 17 and analyzed by TCRb-seq. 2. For LG1233-OVA tumor model, LG1233-OVA sgNT or sgUHRF1 cells were subcutaneously injected into female C57BL/6J mice. Total RNA was extracted from tumor tissues day 27 and analyzed by TCRb-seq.
 
Contributor(s) Tan L, Yin T, Wang L, Mudgal P, Li Q, Wang X
Citation(s) 39362877
Submission date Mar 07, 2024
Last update date Oct 15, 2024
Contact name Liuyang Wang
Organization name Duke University
Street address 213 Research Drive
City Durham
State/province NC
ZIP/Postal code 27710
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (33)
GSM8136389 LT1_LLC-OVA_shNT_IgG_1 (biol rep 1)
GSM8136390 LT2_LLC-OVA_shNT_IgG_2 (biol rep 2)
GSM8136391 LT3_LLC-OVA_shNT_IgG_3 (biol rep 3)
Relations
BioProject PRJNA1085386

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE261146_RAW.tar 65.4 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
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