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Early anti-tumor activity of oral Langerhans cells is compromised by a carcinogen

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE192470 | GEO | 2022/01/26

REPOSITORIES: GEO

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Notch is active in Langerhans Cell Histiocytosis and confers pathognomonic features on dendritic cells.

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