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| Status |
Public on Apr 01, 2024 |
| Title |
Cancer SLC6A6-mediated taurine uptake impairs CD8+ T cell antitumor immunity by upregulating immune checkpoints [mouse RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Taurine is a supplement used to bolster immunity, but how taurine affects antitumor immunity remains largely unknown. We report that SLC6A6-mediated uptake of taurine by gastric cancer (GC) cells results in T cell exhaustion and cancer progression. SLC6A6 was correlated with GC aggressiveness and poor outcomes, and taurine uptake increased GC proliferation, survival, and cell motility. Taurine significantly increased CD8+ T cell infiltration and cytotoxic effector expression in GC tumors. Mechanistically, taurine deprivation in CD8+ T cells increased ER stress and the unfolded protein response, resulting in AT4 transcription, which acts as a switch for T cell exhaustion. SLC6A6 was transactivated by SP1 in GC cells, with a strong correlation between SP1 and SLC6A6 in GC patients. The SP1-SLC6A6 axis was triggered by chemotherapy. Our findings reveal that SLC6A6-mediated taurine consumption impacts immune evasion and propose that taurine supplementation might reinvigorate CD8+ T cell response and enhance therapy efficacy.
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| Overall design |
Single CD45+ immune cells were obtained from taurine-treated MFC tumors from 615 mice and compared to their counterparts in saline-treated tumors.
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| Contributor(s) |
Zhao X, Cao T |
| Citation(s) |
38565142 |
| |
| Submission date |
Dec 04, 2023 |
| Last update date |
Apr 11, 2024 |
| Contact name |
Xiaodi Zhao |
| E-mail(s) |
leedyzhao@fmmu.edu.cn
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| Organization name |
Xijing Hospital of Fourth Military Medical University
|
| Department |
Xijing Hospital of Digestive Diseases
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| Lab |
State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases
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| Street address |
No.127 Changle West Road
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| City |
Xi'an |
| ZIP/Postal code |
710032 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1048446 |
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