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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 10, 2023 |
| Title |
Metabolic Programs of T Cell Tissue Residency Empower Tumor Immunity [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Tissue-resident memory CD8 T cells (TRM) offer fast, robust, and long-term protection at sites of re-infection1. Tumor-infiltrating lymphocytes (TIL) with characteristics of TRM maintain enhanced effector functions, predict responses to immunotherapy, and accompany better prognoses2,3. Thus, an improved understanding of the metabolic strategies that enable tissue residency could inform new approaches to empower T cell responses in tissues and solid tumors. To systematically define the basis for the metabolic reprogramming supporting TRM differentiation, survival, and function, we leveraged in vivo functional genomics, untargeted metabolomics, and transcriptomics of virus-specific memory CD8 T cell populations. We found that memory CD8 T cells deployed a range of adaptations to tissue residency, including a marked reliance on non-steroidal products of the mevalonate/cholesterol pathway, such as Coenzyme Q (CoQ), driven by increased activity of the transcription factor Srebp2. This metabolic adaptation was most pronounced in the small intestine (SI), where TRM interface with dietary cholesterol and maintain a heightened state of activation4, and was shared by functional TIL in diverse tumor types in mice and humans. Enforcing CoQ synthesis through Fdft1 deletion or Pdss2 overexpression promoted mitochondrial respiration, memory formation upon viral infection, and enhanced antitumor immunity. In sum, through a systematic exploration of TRM metabolism, we reveal how these programs can be leveraged to empower CD8 T cell memory formation in the context of acute infections and enhance antitumor immunity.
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| Overall design |
RNAseq of sorted P14 CD8 T cells from mice at day 7 after infection with LCMV. P14 CD8 T cells were isolated from the spleen, liver, kidney and small intestine. All samples but spleen were gated on intravascular-associated negative cells based on in vivo CD8a stain prior to analysis. Every replicate has cells pooled from two mice.
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| Contributor(s) |
Reina-Campos M, W Goldrath A |
| Citation(s) |
37648857 |
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| Submission date |
Jun 27, 2022 |
| Last update date |
Sep 08, 2023 |
| Contact name |
Miguel Reina-Campos |
| E-mail(s) |
[email protected]
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| Organization name |
La Jolla Institute for Immunology
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| Lab |
Reina
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| Street address |
9420 Athena Circle
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| City |
La Jolla |
| State/province |
California |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE207044 |
Metabolic Programs of T Cell Tissue Residency Empower Tumor Immunity |
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| Relations |
| BioProject |
PRJNA853359 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE207043_filtered_feature_bc_matrix.h5 |
12.1 Mb |
(ftp)(http) |
H5 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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