Early antitumor 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 (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.

Single-cell analysis of myeloid cells in HPV+tonsillar cancer

“…MAFB + LCs featured high RUNX3 upregulation, and downregulated the activity of the MAFB regulon on their differentiation into RUNX3 + cDC2s. In line with our results, previous studies have reported expression of MAFB and RUNX3 during LC differentiation in mouse mucosa and skin (57–59). In contrast, RUNX3 − cDC2s most likely represented bona-fide lymphoid organ resident cDC2s, as judged by their exclusive presence in HT, absence in TC and other HNC subtypes, as well as the lack of monocyte lineage markers and regulons at RNA and protein level.…”

Single‐cell transcriptomics reveals a senescence‐associated IL ‐6/ CCR6 axis driving radiodermatitis

“…Additionally, 10% (4/46) of naive αβT/ILC cells were identified as Foxp3 + Tregs (Appendix Fig S4 ). Dendritic cells of Cl‐12 appeared largely of cDC2 ( Itgam , Sirpa ) lineage that cluster together with monocyte‐derived macrophages ( Adgre1 , C1qc , Mafb ; Guilliams et al , 2014 ; Saba et al , 2022 ; Appendix Fig S4 ).…”

“…However, about 10% (5/46) of the cells in the cluster expressed ILC-associated genes (Klrk1, Runx, or Fuca1; Koues et al, 2016) (Appendix Fig S4). Dendritic cells of Cl-12 appeared largely of cDC2 (Itgam, Sirpa) lineage that cluster together with monocyte-derived macrophages (Adgre1, C1qc, Mafb; Guilliams et al, 2014;Saba et al, 2022;Appendix Fig S4).…”

Case Report: Langerhans Cell Sarcoma With Intracranial and Extracranial Communication on the Left Frontal Bone

“…The male:female ratio is approximately 1.3:1, with a slightly higher prevalence in females than males ( 4 ). The cause and pathogenesis of LCS are not known, but reports suggest that they are related to uncontrolled regulation of the immune system and a proliferation disorder of LC ( 5 ). Some cases of LCS may be associated with other tumors, such as follicular lymphoma, adenocarcinoma, and germ-cell tumors, which also occur in patients with schizophrenia who have undergone long-term treatment ( 6 – 8 ).…”