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    Female immunity protects from cutaneous squamous cell carcinoma

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    Authors
    Budden, Timothy
    Gaudy-Marqueste, C.
    Craig, Sarah
    Hu, Y.
    Earnshaw, Charles
    Gurung, Shilpa
    Ra, A.
    Akhras, V.
    Shenjere, Patrick
    Green, R.
    Jamieson, L.
    Lear, J.
    Motta, L.
    Caulin, C.
    Oudit, Deemesh
    Furney, S. J.
    Viros, Amaya
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    Affiliation
    Skin Cancer and Ageing, Cancer Research UK Manchester Institute
    Issue Date
    2021
    
    Metadata
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    Abstract
    Purpose: Cancer susceptibility and mortality are higher in males, and the mutational and transcriptomic landscape of cancer differs by sex. The current assumption is that men are at higher risk of epithelial cancers as they expose more to carcinogens and accumulate more damage than women. We present data showing women present less aggressive primary cutaneous squamous cell carcinoma (cSCC) and early strong immune activation. Methods: We explored clinical and molecular sexual disparity in immunocompetent and immunosuppressed primary cSCC patients (N=738, N=160), advanced stage cSCC (N=63, N=20) andFVB/N mice exposed to equal doses of DMBA, as well as in human keratinocytes by whole exome, bulk and single cell RNA sequencing. Results: We show cSCC is more aggressive in men, and immunocompetent women develop mild cSCC, later in life. To test if sex drives disparity, we exposed male and female mice to equal doses of carcinogen, and found males present more aggressive, metastatic cSCC than females. Critically, females activate cancer immune-related expression pathways and CD4 and CD8 T cell infiltration independently of mutations, a response that is absent in prednisolone treated animals. In contrast, males increase the rate of mitosis and proliferation in response to carcinogen. Women's skin and keratinocytes also activate immune-cancer fighting pathways and immune cells at ultraviolet radiation-damaged sites. Critically, a compromised immune system leads to high-risk, aggressive cSCC specifically in women.
    Citation
    Budden T, Gaudy-Marqueste C, Craig S, Hu Y, Earnshaw C, Gurung S, et al. Female immunity protects from cutaneous squamous cell carcinoma. Clin Cancer Res. 2021.
    Journal
    Clinical Cancer Research
    URI
    http://hdl.handle.net/10541/623910
    DOI
    10.1158/1078-0432.Ccr-20-4261
    PubMed ID
    33795258
    Additional Links
    https://dx.doi.org/10.1158/1078-0432.Ccr-20-4261
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1158/1078-0432.Ccr-20-4261
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