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SRX24948429: GSM8333783: Untreated_DEG_Spleen2; Mus musculus; RNA-Seq
1 ILLUMINA (Illumina NovaSeq 6000) run: 138.8M spots, 9.7G bases, 3.1Gb downloads

External Id: GSM8333783_r1
Submitted by: Love lab, Koch Institute, MIT
Study: Expansion of Tumor-Infiltrating CD8+ T Cell Clonotypes Occurs in the Spleen in Response to Immune Checkpoint Blockade
show Abstracthide Abstract
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.
Sample: Untreated_DEG_Spleen2
SAMN41874904 • SRS21652161 • All experiments • All runs
Organism: Mus musculus
Library:
Name: GSM8333783
Instrument: Illumina NovaSeq 6000
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC SINGLE CELL
Selection: cDNA
Layout: PAIRED
Construction protocol: Prior to staining, cells were washed with FACS staining buffer (chilled PBS containing 1% FBS and 2 mM EDTA). Cells were resuspended in 50 mL of the antibody-containing staining buffer, plus eBioscience Fixable Viability Dye eFluor 780 or eFluor 506 to distinguish live and dead cells and with anti-CD16/CD32 (clone 93, BioLegend) to prevent non-specific antibody binding. Cell surface proteins were stained for 20 min on ice with fluorophore-conjugated antibodies at a 1:200 dilution. Cells were then washed twice and resuspended in eBioscience Fixation/Permeabilization buffer and incubated 30 minutes at room temperature. Cells were then washed twice and resuspended in staining buffer with intracellular antibodies. To obtain absolute counts of cells, Precision Count Beads (BioLegend) were added to samples according to manufacturer's instructions. Flow cytometry sample acquisition was performed on a LSR Fortessa cytometer (BD), and the collected data was analyzed using FlowJo v10.5.3 software (TreeStar). For cell sorting, the surface staining was performed as described above under sterile conditions, and cells were acquired and sorted into complete medium using a FACSAria III sorter (BD). For CD8+ T cell analysis, cells were pre-gated on FSA and SSC, Live, CD45+, CD45-IV-, CD3+ or TCRbeta+, single cells, CD4-, CD8+. Antibodies used: CD4 clone RM4-5, CD45 clone 30-F11, CD45.1 clone A20, CD45.2 clone 104, CD8a clone 53-6.7, TCRb clone H57-597, CD3 clone 17A2, Thy1.2 clone 53-2.1, CXCR3 clone CXCR3-173, CX3CR1 clone SAO11F11, KLRG1 clone 2F1/KLRG1. SIY-tetramer was obtained from the NIH tetramer core, conjugated to PE, and added at 1:500-1:1,000 to the extracellular staining antibody mix. For scRNA-seq experiments with cell hashing, cells were also stained with Totalseq A anti-mouse hashing antibodies (Biolegend) before FACS. Sorted cells were then processed for scRNA-seq using the Seq-Well platform with second strand chemistry, as previously described (63, 64). Whole transcriptome libraries were barcoded and amplified using the Nextera XT kit (Illumina) and were sequenced on a Novaseq 6000 (Illumina). Hashtag oligo libraries were amplified as described previously and were sequenced on a Nextseq 550(38).
Runs: 1 run, 138.8M spots, 9.7G bases, 3.1Gb
Run# of Spots# of BasesSizePublished
SRR29435653138,829,6699.7G3.1Gb2024-07-19

ID:
33284672

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