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| Status |
Public on Jul 11, 2023 |
| Title |
SOCS3 deletion in effector T cells confers an anti-tumorigenic role of IL-6 to the pro-tumorigenic cytokine [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Interleukin (IL)-6 is abundantly expressed in the tumor microenvironment and is associated with poor patient outcomes. Here, we demonstrate that the deletion of the suppressor of cytokine signaling 3 (SOCS3) in T cells potentiates anti-tumor immune responses by conferring the anti-tumorigenic function of IL-6 in mouse and human models. In Socs3-deficient CD8+ T cells, IL-6 upregulates the expression of type I interferon (IFN)-regulated genes and enhances the anti-tumor effector function of T cells, while also modifying mitochondrial fitness to increase mitochondrial membrane potential and reactive oxygen species (ROS) levels and to promote metabolic glycolysis in the energy state. Furthermore, Socs3 deficiency reduces regulatory T cells and increases T helper 1 (Th1) cells. SOCS3 knockdown in human chimeric antigen receptor T (CAR-T) cells exhibits a strong anti-tumor response in humanized mice. Thus, genetic disruption of SOCS3 offers an avenue to improve the therapeutic efficacy of adoptive T cell therapy.
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| Overall design |
MC38 cells, murine colon adenocarcinoma cells, were subcutaneously injected in the flanks of WT Socs3f/f or Cd4Cre Socs3f/f mice. CD3e+ TCRb+ T cells were isolated from tumor mass 12 days after tumor inoculation for scRNAseq analysis.
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| Contributor(s) |
Mise-Omata S, Ando M, Srirat T, Nakagawara K, Hayakawa T, Iizuka-Koga M, Nishimasu H, Nureki O, Ito M, Yoshimura A |
| Citation(s) |
37582370 |
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| Submission date |
Dec 19, 2022 |
| Last update date |
Oct 10, 2023 |
| Contact name |
Setsuko Mise-Omata |
| E-mail(s) |
setsukomise@gmail.com
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| Phone |
+81353633767
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| Organization name |
Keio University
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| Department |
Department of Microbiology and Immunology
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| Lab |
Yoshimura's Laboratory
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| Street address |
35 Shinanomachi
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| City |
Shinjuku-ku |
| State/province |
Tokyo |
| ZIP/Postal code |
1608582 |
| Country |
Japan |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (1) |
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| This SubSeries is part of SuperSeries: |
| GSE235117 |
SOCS3 deletion in effector T cells confers an anti-tumorigenic role of IL-6 to the pro-tumorigenic cytokine |
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| Relations |
| BioProject |
PRJNA913990 |
