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| Status |
Public on Nov 20, 2023 |
| Title |
Single-cell analysis of CD4+ cytotoxic T lymphocytes in human oral squamous cell carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cancer immunotherapy targeting CD8+ T cells has made remarkable progress, even for oral squamous cell carcinoma (OSCC), a heterogeneous epithelial tumor without a substantial increase in the overall survival rate over the past decade. However, the therapeutic effects remain limited due to therapy resistance. Thus, a more comprehensive understanding of the roles of CD4+ T cells and B cells is crucial for more robust development of cancer immunotherapy. In this study, we examined immune responses and effector functions of CD4+ T cells, CD8+ T cells and B cells infiltrating in OSCC lesions using single-cell RNA sequencing analysis, T cell receptor (TCR) and B cell receptor (BCR) repertoire sequencing analysis, and multi-color immunofluorescence staining. Finally, two Kaplan-Meier curves and several Cox proportional hazards models were constructed for the survival analysis. We observed expansion of CD4+ cytotoxic T lymphocytes (CTLs) expressing granzymes, which are reported to induce cell apoptosis, with a unique gene expression patterns. CD4+ CTLs also expressed CXCL13, which is a B cell chemoattractant. Cell-cell communication analysis and multi-color immunofluorescence staining demonstrated potential interactions between CD4+ CTLs and B cells, particularly IgD- CD27- double negative (DN) B cells. Expansion of CD4+ CTLs, DN B cells, and their contacts has been reported in T and B cell-activated diseases, including IgG4-related disease and COVID-19. Notably, we observed upregulation of several inhibitory receptor genes including CTLA-4 in CD4+ CTLs, which possibly dampened T and B cell activity. We next demonstrated comprehensive delineation of the potential for CD8+ T cell differentiation towards dysfunctional states. Furthermore, prognostic analysis revealed unfavorable outcomes of patients with a high proportion of CD4+ CTLs in OSCC lesions. Our study provides a dynamic landscape of lymphocytes and demonstrates a systemic investigation of CD4+ CTL effects infiltrating into OSCC lesions, which may share some pathogenesis reported in severe T and B cell-activated diseases such as autoimmune and infectious diseases.
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| Overall design |
In this study, we examined immune responses and effector functions of CD4+ T cells, CD8+ T cells and B cells infiltrating in OSCC lesions via single-cell RNA sequencing analysis, T cell receptor (TCR) and B cell receptor (BCR) repertoire sequencing analysis from 10x chromium using samples from three OSCC patients.
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| Contributor(s) |
Chen H, Sameshima J, Yokomizo S, Sueyoshi T, Nagano H, Miyahara Y, Sakamoto T, Fujii S, Kiyoshima T, Guy T, Nakamura S, Moriyama M, Kaneko N, Kawano S |
| Citation(s) |
38077321 |
| BioProject |
PRJNA1039158 |
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| Submission date |
Nov 13, 2023 |
| Last update date |
Dec 14, 2023 |
| Contact name |
Hu Chen |
| E-mail(s) |
[email protected]
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| Organization name |
Kyushu University
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| Department |
Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science
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| Street address |
3-1-1 Maidashi, Higashi-ku
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| City |
Fukuoka |
| ZIP/Postal code |
812-8582 |
| Country |
Japan |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (3) |
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| Supplementary file |
Size |
Download |
File type/resource |
| GSE247582_RAW.tar |
100.6 Mb |
(http)(custom) |
TAR (of CSV, MTX, TSV) |
| GSE247582_counts.tar.gz |
100.7 Mb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
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