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Status |
Public on Jan 26, 2022 |
Title |
Early anti-tumor activity of oral Langerhans cells is compromised by a carcinogen |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Early diagnosis of oral squamous cell carcinoma (OSCC) remains an unmet clinical need. Therefore, elucidating the initial events of OSCC preceding tumor development could benefit OSCC prognosis. Here we define the Langerhans cells (LC) of the tongue and demonstrate that LC protect the epithelium from carcinogen-induced OSCC by rapidly priming αβT cells capable of eliminating γH2AX+ epithelial cells, whereas γδT and NK cells are dispensable. The carcinogen, however, dysregulates the epithelial resident mononuclear phagocytes, reducing LC frequencies while dendritic cells (DC), macrophages, and plasmacytoid DC (pDC) populate the epithelium. Single-cell RNAseq analysis indicates that these newly differentiated cells display an immunosuppressive phenotype accompanied by an expansion of T regulatory (Treg) cells. Accumulation of the Treg cells was regulated, in part, by pDC and precedes the formation of visible tumors. This suggests LC play an early protective role during OSCC, yet the capacity of the carcinogen to dysregulate the differentiation of mononuclear phagocytes facilitates oral carcinogenesis.
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Overall design |
The mice were treated with the carcinogen 4NQO in the drinking water to induce carcinogenesis in the tongue epithelium, the scRNAseq analysis was performed on cells purified from the tongue epithelium after enrichment to CD45+ cells.
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Contributor(s) |
Hovav A, Yona S, Saba Y, David E |
Citation(s) |
35012988 |
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Submission date |
Dec 22, 2021 |
Last update date |
Jan 27, 2022 |
Contact name |
Ido Amit |
E-mail(s) |
[email protected]
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Phone |
972-8-9343338
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Organization name |
Weizmann Institute of Science
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Department |
Immunology
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Street address |
234 Herzl st.
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City |
Rehovot |
ZIP/Postal code |
760001 |
Country |
Israel |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (2) |
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Relations |
BioProject |
PRJNA791624 |
Supplementary file |
Size |
Download |
File type/resource |
GSE192470_RAW.tar |
44.3 Mb |
(http)(custom) |
TAR (of TAR) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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