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| Status |
Public on Jan 22, 2025 |
| Title |
Molecular landscape of tumor-associated tissue-resident memory T cells in tumor microenvironment of hepatocellular carcinoma [HCC_scTCR] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Immunotherapy for liver cancer is used to rejuvenate tumor-infiltrating lymphocytes by modulating the immune microenvironment. Thus, early protective functions of T cell subtypes with tissue-specific residency have been studied in the tumor microenvironment (TME). We identified tumor-associated tissue-resident memory T (TA-TRM) cells in hepatocellular carcinoma (HCC) and characterized their molecular signatures. We obtained single-cell RNA and single-cell TCR sequencing data from five patients with HCC. The heterogeneous characteristics of TRM cell subsets within the TME were then investigated and validated. We characterized two TRM clusters (CD69+ and CD103+) that expressed unique signature genes and validated their similar molecular patterns in an independent dataset. Risk scores based on core gene expression in TA-TRM cells were associated with survival in both datasets. Trajectory analysis revealed that the two lineages followed different trajectory paths with distinct marker gene expression across pseudo-time. CD103+ TA-TRM cells showed diverse clonotypes and shared clonotypes with other cell groups. Lower clonal diversity and distinct signaling interactions were observed in the recurrent than in the non-recurrent samples. The CXCL13-CXCR3 interaction between CD103+ TA-TRM and regulatory T cells was observed only in the recurrent samples. We identified two subtypes of TA-TRM cells in HCC and demonstrated their unique molecular signatures, relevance to survival, and distinct signaling networks according to recurrence. The study findings provide a better understanding of the molecular characteristics of TA-TRM cells in HCC and potential immunotherapeutic strategies.
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| Overall design |
We generated scRNA-seq of CD45+ immune cells from tumors and adjacent livers for HCC by fluorescence-activated cell sorting (FACS).
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Submitter declares that the raw data cannot be provided due to patient privacy concerns.
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| Web link |
https://doi.org/10.1186/s12964-025-02070-w
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| Contributor(s) |
Park M, Jo H, Kim H, Kim J, Park W, Paik Y, Yoon Y, Kang W, Won H |
| Citation(s) |
39934824 |
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| Submission date |
Nov 05, 2024 |
| Last update date |
Apr 24, 2025 |
| Contact name |
Hong-Hee Won |
| E-mail(s) |
wonhh@skku.edu
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| Organization name |
SungKyunKwan University
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| Street address |
81, Irwon-ro
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| City |
Gangnam-gu |
| ZIP/Postal code |
06351 |
| Country |
South Korea |
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| Platforms (3) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
| GPL30209 |
MGISEQ-2000RS (Homo sapiens) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA1182296 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE281111_HCC_M1_LIL_demuxlet.best.gz |
1.3 Mb |
(ftp)(http) |
BEST |
| GSE281111_RAW.tar |
1.3 Mb |
(http)(custom) |
TAR (of CSV) |
| Raw data not provided for this record |
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