Authors
Budden, TimothyGaudy-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
Affiliation
Skin Cancer and Ageing, Cancer Research UK Manchester InstituteIssue Date
2021
Metadata
Show full item recordAbstract
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 ResearchDOI
10.1158/1078-0432.Ccr-20-4261PubMed ID
33795258Additional Links
https://dx.doi.org/10.1158/1078-0432.Ccr-20-4261Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1158/1078-0432.Ccr-20-4261
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