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Monocytes promote UV‐induced epidermal carcinogenesis


Lelios, Iva; Stifter, Sebastian A; Cecconi, Virginia; Petrova, Ekaterina; Lutz, Mirjam; Cansever, Dilay; Utz, Sebastian G; Becher, Burkhard; van den Broek, Maries; Greter, Melanie (2021). Monocytes promote UV‐induced epidermal carcinogenesis. European Journal of Immunology, 51(7):1799-1808.

Abstract

Mononuclear phagocytes consisting of monocytes, macrophages, and DCs play a complex role in tumor development by either promoting or restricting tumor growth. Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer arising from transformed epidermal keratinocytes. While present at high numbers, the role of tumor-infiltrating and resident myeloid cells in the formation of cSCC is largely unknown. Using transgenic mice and depleting antibodies to eliminate specific myeloid cell types in the skin, we investigated the involvement of mononuclear phagocytes in the development of UV-induced cSCC in K14-HPV8-E6 transgenic mice. Although resident Langerhans cells were enriched in the tumor, their contribution to tumor formation was negligible. Equally, dermal macrophages were dispensable for the development of cSCC. In contrast, mice lacking circulating monocytes were completely resistant to UV-induced cSCC, indicating that monocytes promote tumor development. Collectively, these results demonstrate a critical role for classical monocytes in the initiation of skin cancer.

Abstract

Mononuclear phagocytes consisting of monocytes, macrophages, and DCs play a complex role in tumor development by either promoting or restricting tumor growth. Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer arising from transformed epidermal keratinocytes. While present at high numbers, the role of tumor-infiltrating and resident myeloid cells in the formation of cSCC is largely unknown. Using transgenic mice and depleting antibodies to eliminate specific myeloid cell types in the skin, we investigated the involvement of mononuclear phagocytes in the development of UV-induced cSCC in K14-HPV8-E6 transgenic mice. Although resident Langerhans cells were enriched in the tumor, their contribution to tumor formation was negligible. Equally, dermal macrophages were dispensable for the development of cSCC. In contrast, mice lacking circulating monocytes were completely resistant to UV-induced cSCC, indicating that monocytes promote tumor development. Collectively, these results demonstrate a critical role for classical monocytes in the initiation of skin cancer.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Uncontrolled Keywords:Immunology, Immunology and Allergy
Language:English
Date:July 2021
Deposited On:11 May 2021 13:18
Last Modified:24 Feb 2024 02:50
Publisher:Wiley-VCH Verlag
ISSN:0014-2980
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/eji.202048841
PubMed ID:33759186
Project Information:
  • : FunderSNSF
  • : Grant ID310030_175565
  • : Project TitleImpact of radiotherapy-induced inflammation on local tumor-specific immunity and metastasis
  • : FunderSNSF
  • : Grant ID310030_170320
  • : Project TitleThe role of the NF-kappa B inducing kinase NIK in central T cell tolerance and peripheral immune regulation
  • : FunderSNSF
  • : Grant ID316030_150768
  • : Project TitleThe use of Mass-cytometry in multi-parameter immune cell analysis
  • : FunderSNSF
  • : Grant IDPP00P3_144781
  • : Project TitleThe role of interleukin-34 for the development and function of the mononuclear phagocyte system during the steady state and inflammation
  • : FunderSNSF
  • : Grant IDPP00P3_179059
  • : Project TitleThe Role of the Mononuclear Phagocyte System In Inflammation Induced Tumor Development
  • : FunderSNSF
  • : Grant IDCRSII5_177208
  • : Project TitleDefining the identity and differentiation pathways of the immune-stimulating fibroblastic tumor stroma
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)