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| Status |
Public on Jul 08, 2024 |
| Title |
Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in Colorectal Cancer |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Expanding the efficacy of immune checkpoint blockade (ICB) in colorectal cancer (CRC) patients presses for a comprehensive understanding of treatment responsiveness. Here, we analyzed 169 single-cell samples from CRC patients at multiple sequential time points during the course of anti-PD-1 neoadjuvant therapy to map the evolution of local and systemic immunity. In tumors, exhausted T (Tex) cells or tumor-reactive-like CD8 T (Ttr-like) cells were closely related to treatment efficacy, and we observed correlated dynamics between Tex cells and multiple other tumor-enriched cell types following the treatment. Accordingly, several coordinated cellular programs exhibiting distinct response associations were identified. From a systemic perspective, we found divergent replenishment patterns of Ttr-like cells underlying different response statuses and decoded the phenotypic transitions of Ttr-like cells as they infiltrated tissues from the periphery. Finally, a predictive signature was established using circulating CD8 T cells. Our study provides novel insights into the spatiotemporal cellular dynamics following PD-1 blockade in CRC.
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| Overall design |
Leveraging single-cell RNA-seq and TCR-seq technologies, we generated single-cell transcriptome profiles of primary tumor tissues, adjacent normal tissues, and peripheral blood of 22 CRC patients underwent neoadjuvant anti-PD-1 treatment. Raw sequence data were provided at: China Genomic Sequence Archive (GSA), and we will provide the accession number once the paper is accepted. **Raw data will be uploaded to China Genomic Sequence Archive (GSA), according to the Regulations on the Management of Human Genetic Resources in China.**
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| Contributor(s) |
Chen Y, Wang D, Li Y, Wu A, Zhang Z |
| Citation(s) |
38981439 |
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| Submission date |
Jul 05, 2023 |
| Last update date |
Jul 29, 2024 |
| Contact name |
Zemin Zhang |
| E-mail(s) |
zemin@pku.edu.cn
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| Organization name |
Peking University
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| Department |
BIOPIC
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| Lab |
Zemin Zhang's Lab
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| Street address |
Yiheyuan Road
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| City |
Beijing |
| State/province |
Beijing |
| ZIP/Postal code |
100091 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (169)
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| Relations |
| BioProject |
PRJNA991601 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE236581_CRC-ICB_metadata.txt.gz |
12.7 Mb |
(ftp)(http) |
TXT |
| GSE236581_VDJ_merge.txt.gz |
43.0 Mb |
(ftp)(http) |
TXT |
| GSE236581_barcodes.tsv.gz |
4.5 Mb |
(ftp)(http) |
TSV |
| GSE236581_counts.mtx.gz |
3.9 Gb |
(ftp)(http) |
MTX |
| GSE236581_features.tsv.gz |
243.5 Kb |
(ftp)(http) |
TSV |
| Raw data not provided for this record |
| Processed data are available on Series record |
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