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Circulating Immunosuppressive Regulatory T Cells Predict Risk of Incident Cutaneous Squamous Cell Carcinoma
Dana E Rollison1, Jane L Messina2, Basil S Cherpelis3
1Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, United States.
Frontiers in Medicine
|November 19, 2021
Summary
Higher levels of circulating CCR4-high regulatory T cells (Tregs) predict increased risk of cutaneous squamous cell carcinoma (cuSCC), especially with high UVR exposure. This finding may inform cuSCC screening and prevention strategies.
Area of Science:
- Immunology
- Dermatology
- Oncology
Background:
- Ultraviolet radiation (UVR) is a known risk factor for cutaneous squamous cell carcinoma (cuSCC).
- UVR exposure is linked to increased circulating immunosuppressive regulatory T cells (Tregs), but their role in cuSCC development is unclear.
Purpose of the Study:
- To investigate the association between circulating Treg levels and cuSCC development.
- To determine if this association is modified by UVR exposure.
Main Methods:
- Prospective cohort study of 327 immunocompetent individuals with baseline UVR and Treg measurements.
- Flow cytometry used to quantify distinct Treg phenotypes (CCR4hi, CLA+).
- Immunohistochemistry assessed Tregs and solar elastosis in cuSCC tumors.
Main Results:
- Higher baseline levels of circulating CCR4hi Tregs significantly predicted incident cuSCC.
- Individuals with high CCR4hi Tregs and high UVR were four times more likely to develop cuSCC (HR=4.11).
- Within cuSCC tumors, CCR4hi Tregs correlated positively with solar elastosis.
Conclusions:
- Elevated CCR4hi peripheral Tregs are a predictor of cuSCC development up to 4 years post-assessment.
- This predictive value is amplified in individuals with high UVR exposure.
- Understanding Treg biology in UVR-induced skin damage may offer new avenues for cuSCC screening, prevention, and treatment.
