 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 19, 2024 |
| Title |
Expansion of Tumor-Infiltrating CD8+ T Cell Clonotypes Occurs in the Spleen in Response to Immune Checkpoint Blockade |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
|
| Summary |
Immune checkpoint blockade (ICB) enhances tumor-reactive T cell responses against cancer, leading to long-term tumor control and survival in a fraction of patients. Given the increasingly recognized complexity of CD8+ T cell differentiation that occurs in response to chronic antigen stimulation, it remains unclear precisely which T cell differentiation states are critical for the response to ICB, as well as the anatomic sites at which ICB-mediated reinvigoration of these T cells occurs. We used paired single-cell RNA and T cell receptor (TCR) sequencing to profile endogenous, tumor-reactive CD8+ T cells isolated from tumors, tumor-draining lymph nodes, and spleens of mice treated with ICB. We identified an intermediate-exhausted population of T cells in the spleen which underwent the greatest expansion in response to ICB and gave rise to the majority of tumor-infiltrating clonotypes. Increasing concentrations of systemic antigen perturbed the differentiation of this phenotype towards an exhausted_KLR state, while a lack of cross-presentation of tumor-derived antigen blunted differentiation in the spleen. We identified an analogous population of exhausted_KLR CD8+ T cells in matched human tumor and blood samples that exhibited diminished tumor-trafficking ability. Collectively, our data demonstrate the critical role of antigen density within the spleen in coordinating the differentiation and expansion of tumor-infiltrating T cell clonotypes in response to ICB.
|
| |
|
| Overall design |
Single-cell whole transcriptome and TCR profiling was performed on endogeneous, SIY-reactive cells isolated from the tumor, lymph node, and spleen of untreated mice and mice undergoing treatment with checkpiont blockade immunotherapy.
|
| |
|
| Contributor(s) |
Morgan DM, Horton BL, Bhandakar V, Van R, Dinter T, Zagorulya M, Love JC, Spranger S |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Jun 17, 2024 |
| Last update date |
Aug 14, 2024 |
| Contact name |
Duncan Matthew Morgan |
| E-mail(s) |
dmmorgan@mit.edu
|
| Organization name |
MIT
|
| Department |
Koch Institute
|
| Lab |
Love lab
|
| Street address |
500 Main St
|
| City |
CAMBRIDGE |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL21626 |
NextSeq 550 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (29)
|
|
| Relations |
| BioProject |
PRJNA1124914 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE270050_RAW.tar |
990.5 Mb |
(http)(custom) |
TAR (of TAB, TSV, TXT) |
| GSE270050_txImport_processed.txt.gz |
974.3 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...