Monocytes promote UV-induced epidermal carcinogenesis

Area of Science:

• Immunology
• Dermatology
• Oncology

Background:

• Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells (DCs), have complex roles in tumor development.
• Cutaneous squamous cell carcinoma (cSCC) is a common nonmelanoma skin cancer originating from epidermal keratinocytes.
• The specific roles of myeloid cells in cSCC formation are not well understood.

Purpose of the Study:

• To investigate the involvement of mononuclear phagocytes in UV-induced cSCC development.
• To elucidate the distinct roles of resident and infiltrating myeloid cells in skin cancer initiation.

Main Methods:

• Utilized K14-HPV8-E6 transgenic mice for UV-induced cSCC model.
• Employed depleting antibodies to eliminate specific myeloid cell populations (Langerhans cells, dermal macrophages, circulating monocytes).
• Assessed the impact of myeloid cell depletion on cSCC development.

Main Results:

• Resident Langerhans cells and dermal macrophages were found to be dispensable for cSCC development.
• Mice lacking circulating monocytes were completely resistant to UV-induced cSCC.
• Circulating monocytes were identified as critical promoters of skin cancer initiation.

Conclusions:

• Classical monocytes play a critical role in the initiation of UV-induced cutaneous squamous cell carcinoma.
• Targeting monocytes may represent a therapeutic strategy for preventing skin cancer development.