ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Female Immunity Protects from Cutaneous Squamous Cell Carcinoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- An estrogen receptor/E2F1/CDKN3 axis protects from UV-induced skin cancers in females.EMBO reports · 2026Article
- Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion.Nature metabolism · 2026Article
- Sex-based immune differences influence tumor progression in head and neck squamous cell carcinoma.Oral oncology · 2026Article
- A highly resolved integrated single-cell atlas of HPV-negative head and neck cancer.Communications medicine · 2026Article
- Mechanisms of immunotherapy in cutaneous squamous cell carcinoma in the tumor microenvironment.Frontiers in immunology · 2025Review
- Article
- Sex as a Predictor of Response to Immunotherapy in Advanced Cutaneous Squamous Cell Carcinoma.Cancers · 2023Article
- Biological differences underlying sex and gender disparities in bladder cancer: current synopsis and future directions.Oncogenesis · 2023Review
- Personalised decision making to predict absolute metastatic risk in cutaneous squamous cell carcinoma: development and validation of a clinico-pathological model.EClinicalMedicine · 2023Article
- Sex Disparity for Patients with Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Systematic Review.Cancers · 2022Review
- A tEMTing target? Clinical and experimental evidence for epithelial-mesenchymal transition in the progression of cutaneous squamous cell carcinoma (a scoping systematic review).Discover oncology · 2022Article
- Defining the incidence of cutaneous squamous cell carcinoma in coastal NSW Australia.The Australasian journal of dermatology · 2022Article
- Emerging precision diagnostics in advanced cutaneous squamous cell carcinoma.NPJ precision oncology · 2022Review
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 5 countries.
Funding
Abstract
purposeCancer 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 with less aggressive primary cutaneous squamous cell carcinoma (cSCC) and early strong immune activation. EXPERIMENTAL
designWe explored clinical and molecular sexual disparity in immunocompetent and immunosuppressed patients with primary cSCC (
resultsWe show cSCC is more aggressive in men, and immunocompetent women develop mild cSCC, later in life. To test whether sex drives disparity, we exposed male and female mice to equal doses of carcinogen, and found males present with 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 UV radiation-damaged sites. Critically, a compromised immune system leads to high-risk, aggressive cSCC specifically in women.
conclusionsThis work shows the immune response is sex biased in cSCC and highlights female immunity offers greater protection than male immunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.