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GEO help: Mouse over screen elements for information. |
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Status |
Public on Jun 30, 2022 |
Title |
High-dimensional single cell analysis of T cells infiltrating human intrahepatic cholangiocarcinoma [RNA-Seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
In tumors, CD4+ T regulatory cells (Tregs), a specialized subtype of cells indispensable for maintaining immune homeostasis and tolerance, inhibit anti-tumor immunity and response to immunotherapy. Selective targeting of the hyperactive Tregs promote tumor regression and synergizes with checkpoint blockade without severe, systemic autoimmunity, that is otherwise observed with non-specific Treg depletion. However, is poorly defined how Treg hyper-activation regulated in the tumor microenvironment. We found that mesenchyme homeobox-1 (MEOX1) a transcription factor with an important role in skeleton formation during development, is specifically overexpressed by intrahepatic cholangiocarcinoma infiltrating Treg compared to Treg cells present in the peritumoral tissue. Integration of transcriptomic data revealed that MEOX1 positively regulates several molecules involved in immunosuppression, including CTLA-4, ICOS and IL10, as well as a tumor Treg-specific signature associated with disease progression. Thus, interfering with the MEOX1-dependent molecular program may represent a novel immunotherapeutic approach capable to block immunosuppression in the tumor microenvironment without inducing autoimmunity in peripheral tissues.
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Overall design |
Transcriptional profiling of human activated Tregs overexpressing MEOX1.
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Web link |
https://doi.org/10.1016/j.jhep.2022.05.043
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Contributor(s) |
Termanini A, Alvisi G, Soldani C, Portale F, Carriero R, Pilipow K, Costa G, Polidoro M, Franceschini B, Malenica I, Puccio S, Lise V, Galletti G, Zanon V, Colombo F, De Simone G, Tufano M, Aghemo A, Di Tommaso L, Peano C, Cibella J, Iannacone M, Roychoudhuri R, Manzo T, Donadon M, Torzilli G, Kunderfranco P, Di Mitri D, Lugli E, Lleo A |
Citation(s) |
35738508 |
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Submission date |
Apr 12, 2021 |
Last update date |
Jul 05, 2022 |
Contact name |
Alberto Termanini |
E-mail(s) |
[email protected]
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Organization name |
Istituto Clinico Humanitas
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Lab |
Bioinformatic Unit
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Street address |
Via Manzoni, 113
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City |
Rozzano |
State/province |
MI |
ZIP/Postal code |
20089 |
Country |
Italy |
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Platforms (1) |
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Samples (6)
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This SubSeries is part of SuperSeries: |
GSE171900 |
Hyperactivated Tregs abundantly infiltrate human intrahepatic cholangiocarcinoma and are controlled by transcription factor MEOX1 |
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Relations |
BioProject |
PRJNA721371 |
SRA |
SRP314461 |
Supplementary file |
Size |
Download |
File type/resource |
GSE171895_RAW.tar |
3.5 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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