Oral Presentation Skin Cancer 2024

Chronic UVB exposure induces early transcriptomic changes associated with skin cancer development (#227)

Chenhao Zhou 1 2 , Jack Galbraith 1 , Edwige Roy 1 , Janin Chandra 1 , Quan Nguyen 2 3 , Graeme Walker 1 , Kiarash Khosrotehrani 1 4
  1. The University of Queensland Frazer Institute, Woolloongabba, QLD, Australia
  2. Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia
  3. QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
  4. Princess Alexandra Hospital, Brisbane, QLD, Australia

Exposure to ultraviolet B rays (UVB) is one of the main risk factors for developing cutaneous squamous cell carcinoma (SCC). Whether chronically UV irradiated skin with repeated suberythemal (low) doses can alter skin biology as reflected in transcriptional changes is unknown. We examined the single-cell and spatial transcriptomic profiles of murine skin exposed to chronic low-dose UVB. Compared to non-exposed control skin, UVB-exposed skin exhibited an increased basal/differentiated keratinocytes (KCs) ratio and a higher abundance of sebaceous glands and T cell infiltrates. The increase in T cell infiltrate was largely attributed to the rise in ILC2-like T cells. Downregulation of Il34-Csf1r ligand-receptor pair in UVB skin predicted impaired communication between KCs and Langerhans cells (LCs), corresponding to the diminished KC-LC spatial co-localization and a shift towards an immature LC phenotype in UVB skin. Dysregulated Il34-Csf1r signaling axis was consistently observed in precancerous skin lesions, chronically UV-exposed human healthy skin and SCC patients through analysis of single cell and spatial transcriptomics of patient samples. Thus, targeting key molecular changes induced by UVB represents a promising approach for early prevention of SCC. Our experimental models enable further evaluation of the targeted therapy of IL-34/CSF1R, which may inform the next-generation immunotherapy trials.