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| Status |
Public on Apr 05, 2024 |
| Title |
Antitumor progenitor exhausted CD8 T cells are sustained with TCR engagement [WGBS] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Durability of an antitumor immune response is mediated in part by the persistence of progenitor exhausted CD8 T cells (Tpex). Tpex serve as a source for the pool of effector T cells, and in the absence of their cognate antigen, they are able to preserve their quantity through a process of self-renewal. However, it remains unknown how TCR engagement impacts the self-renewal capacity of Tpex in settings of continued antigen exposure. Here, we used a Lewis lung carcinoma model that elicits an optimal or attenuated TCR signal in CD8 T cells to investigate its effect on Tpex persistence during tumor development. Longitudinal phenotyping and single-cell transcriptomics of tumor-specific T cells revealed that formation of the Tpex reservoir in tumor-draining lymph nodes, and its subsequent replenishment of intratumoral Tpex, is dependent on optimal TCR engagement. Notably, adoptive transfer of optimally primed Tpex into a tumor setting with attenuated TCR stimulation significantly accelerates their terminal differentiation, contrasting to the sustained self-renewal occuring with optimal TCR stimulation. This TCR-reinforced Tpex development and self-renewal is coupled to proximal positioning to dendritic cell niches and epigenetic imprinting that involves increased chromatin accessibility at Egr2 and Tcf1 target loci. Collectively, our study highlights the critical role of TCR engagement in sustaining Tpex during tumor progression
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| Overall design |
3 replicates of LN_M9 samples, 3 replicates of LN_C6M9 samples, 1 replicate each of TU_M9, TU_C6M9, TU_M9_TIM3+, TU_M9_TIM3-, TU_C6M9_TIM3+, TU_C6M9_TIM3- samples
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| Contributor(s) |
Lan X, Youngblood B |
| Citation(s) |
38816618 |
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| Submission date |
Mar 29, 2024 |
| Last update date |
May 31, 2024 |
| Contact name |
Tian Mi |
| E-mail(s) |
tmi@stjude.org
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| Organization name |
St. Jude Children's Research Hospital
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| Department |
Immunology
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| Street address |
262 Danny Thomas Pl MS351
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| GSM8180307 |
LN_C6M9 Day 8, replicate 1, WGBS |
| GSM8180308 |
TU_M9_TIM3- Day 8, WGBS |
| GSM8180309 |
TU_M9_TIM3+ Day 8, WGBS |
| GSM8180310 |
TU_C6M9_TIM3- Day 8, WGBS |
| GSM8180311 |
TU_C6M9_TIM3+ Day 8, WGBS |
| GSM8180312 |
LN_M9 Day 8, replicate 2, WGBS |
| GSM8180313 |
LN_C6M9 Day 8, replicate 2, WGBS |
| GSM8180314 |
LN_M9 Day 8, replicate 3, WGBS |
| GSM8180315 |
LN_C6M9 Day 8, replicate 3, WGBS |
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| This SubSeries is part of SuperSeries: |
| GSE262845 |
Antitumor progenitor exhausted CD8 T cells are sustained with TCR engagement |
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| Relations |
| BioProject |
PRJNA1093469 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE262843_RAW.tar |
1.2 Gb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
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