| First Author | Saba Y | Year | 2022 |
| Journal | Proc Natl Acad Sci U S A | Volume | 119 |
| Issue | 3 | PubMed ID | 35012988 |
| Mgi Jnum | J:320243 | Mgi Id | MGI:6870484 |
| Doi | 10.1073/pnas.2118424119 | Citation | Saba Y, et al. (2022) Early antitumor activity of oral Langerhans cells is compromised by a carcinogen. Proc Natl Acad Sci U S A 119(3):e2118424119 |
| abstractText | 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 (LCs) of the tongue and demonstrate that LCs protect the epithelium from carcinogen-induced OSCC by rapidly priming alphabetaT cells capable of eliminating gammaH2AX(+) epithelial cells, whereas gammadeltaT and natural killer cells are dispensable. The carcinogen, however, dysregulates the epithelial resident mononuclear phagocytes, reducing LC frequencies, while dendritic cells (DCs), macrophages, and plasmacytoid DCs (pDCs) populate the epithelium. Single-cell RNA-sequencing 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 pDCs and precedes the formation of visible tumors. This suggests LCs play an early protective role during OSCC, yet the capacity of the carcinogen to dysregulate the differentiation of mononuclear phagocytes facilitates oral carcinogenesis. |
