Early antitumor activity of oral Langerhans cells is compromised by a carcinogen

Yasmin Saba, Itay Aizenbud, Daniela Matanes, Noam Koren, Or Barel, Khalid Zubeidat, Tal Capucha, Eyal David, Luba Eli-Berchoer, Patrizia Stoitzner, Asaf Wilensky, Ido Amit, Rakefet Czerninski, Simon Yona*, Avi Hai Hovav*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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 (LCs) of the tongue and demonstrate that LCs protect the epithelium from carcinogen-induced OSCC by rapidly priming αβT cells capable of eliminating γH2AX+ epithelial cells, whereas γδT 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.

Original languageAmerican English
Article numbere2118424119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number3
DOIs
StatePublished - 18 Jan 2022

Bibliographical note

Publisher Copyright:
© This article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).

Keywords

  • 4NQO
  • Langerhans cells
  • Oral cancer

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