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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 26, 2022 |
| Title |
Spatiotemporal co-dependency between macrophages and exhausted CD8+ T cells (RNA-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
T cell exhaustion is a major impediment to anti-tumor immunity. However, it remains elusive how other immune cells in the tumor microenvironment (TME) contribute to this dysfunctional state. Here we show that the biology of tumor-associated macrophages (TAM) and exhausted T cells (Tex) in the TME is extensively linked. We demonstrate that in vivo depletion of TAM reduces exhaustion programs in tumor-infiltrating CD8+ T cells and reinvigorates their effector potential. Reciprocally, transcriptional and epigenetic profiling reveals that Tex express factors that actively recruit monocytes to the TME and shape their differentiation. Using lattice light sheet microscopy, we show that TAM and CD8+ T cells engage in unique long-lasting antigen-specific synaptic interactions that fail to activate T cells, but prime them for exhaustion, which is then accelerated in hypoxic conditions. Spatially resolved sequencing supports a spatiotemporal self-enforcing positive feedback circuit that is aligned to protect rather than destroy a tumor.
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| Overall design |
Bulk RNAseq on naïve, effector and exhausted (after day 4 and day 14) OT-I T cells isolated from mouse B78ChOVA melanomas.
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| Contributor(s) |
Kersten K, Hu KH, Combes AJ, Samad B, Harwin T, Ray A, Rao AA, Cai E, Marchuk K, Artichoker J, Courau T, Shi Q, Belk J, Satpathy AT, Krummel MF |
| Citation(s) |
35623342 |
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| Submission date |
Apr 19, 2022 |
| Last update date |
Apr 24, 2023 |
| Contact name |
Arjun Arkal Rao |
| E-mail(s) |
arjunarkal.rao@ucsf.edu
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| Organization name |
University of California, San Francisco
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| Department |
CoLabs
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| Lab |
Data Sciences CoLab
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| Street address |
505 Parnassus Ave, S-447
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94143 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE201074 |
Spatiotemporal co-dependency between macrophages and exhausted CD8+ T cells |
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| Relations |
| BioProject |
PRJNA828180 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE201071_RAW.tar |
3.9 Mb |
(http)(custom) |
TAR (of TAB) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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