Female Immunity Protects from Cutaneous Squamous Cell Carcinoma

The Skin Cancer and Ageing group’s research using mouse models and patient data revealed innate sex-linked biological mechanisms in the immune response that underpins the sex bias observed in incidence and outcome. In response to equal carcinogen dose and mutation burden, female mice had lower incidence and grade of tumours, driven by a higher influx of T cells and upregulation of anti-tumour immune pathways in the skin.

The group confirmed overlapping immune pathways in single cell sequencing of human skin from female cSCC patients, validating the stronger female immune response in the skin to carcinogens in humans. The importance of the immune system protecting against skin cancer was reinforced in a clinical audit of immunosuppressed and immunocompetent cSCC patients by sex. While in the immunocompetent population females had less severe disease and incidence than their male counterparts, in the immunosuppressed population both men and women had equal rates of skin cancer.

Overall, this work establishes that the sex bias in skin cancer is a result of the stronger response of female immunity protecting against tumourigenesis. Further understanding of the role of the immune system in cancer sex bias will impact potential therapy and preventative treatment in at risk populations and allow for patient stratification by risk of disease and progression. Critically, their research shows the importance of including both sexes in models for translational research, particularly for research involving immuno-oncology.