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| Status |
Public on Jul 01, 2022 |
| Title |
Single cell profiling of γδ hepatosplenic T-cell lymphoma unravels tumor cell heterogeneity associated with disease progression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Hepatosplenic T-cell lymphoma (HSTCL) is a rare but very aggressive lymphoma mostly derived from γδ T cells. The molecular pathogenesis driving HSTCL is largely unknown while only limited treatment options are available with poor outcomes. In this study, we performed paired single cell RNA-seq and T cell receptor (TCR) sequencing on biopsies collected from a HSTCL patient pre- and post- chemotherapy treatments. We characterized unique gene expressing signatures of malignant γδ T cells with a set of marker genes were newly identified in HSTCL (AREG, PLEKHA5, VCAM1 etc.). Although the malignant cells were expanded from a single TCR clonotype according to their TCR sequences, they evolved into two transcriptional distinct tumor subtypes during the disease progression. The Tumor_1 subtype was dominant in pre-treatment samples with highly aggressive phenotypes. The Tumor_2 had relative mild cancer hallmark signatures but expressed genes associated with survival and drug resistance (IL32, TOX2, AIF1, AKAP12 etc.), and finally became the major tumor subtype post-treatment. We further dissected the tumor microenvironment of the HSTCL and found CD8 memory T cells were clonal expanded post-treatment. In addition, we discovered dynamically rewiring cell-cell interaction networks during the treatment. The tumor cells had reduced interactions with the microenvironment post-treatment. Our study reveals heterogenous and dynamic tumor and microenvironment underlying pathogenesis of HSTCL and may contribute to identify novel targets for diagnosis and cure of HSTCL in the future.
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| Overall design |
Bone marrow and PBMC biopsies were collected from a HSTCL patient pre- and post- chemotherapies. Samples were proceed for single cell RNA-seq and T cell receptor sequencing
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| Contributor(s) |
Zhang R, Song W, Shi K, Zhang H |
| Citation(s) |
36417130 |
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| Submission date |
Jan 07, 2022 |
| Last update date |
Jan 03, 2023 |
| Contact name |
Ruoyu Zhang |
| E-mail(s) |
[email protected]
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| Organization name |
Innovec Biotherapeutics
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| Street address |
Life Science Park building 1 B220
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| City |
Beijing |
| ZIP/Postal code |
102206 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA795454 |
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