Abstract 4960: Recent ultraviolet radiation exposure and circulating immunosuppressive T-regulatory cells

Abstract

Abstract Background: Ultraviolet radiation exposure (UVR) is a risk factor for several different cancer types. While the mutagenicity of UVR is well-documented, UVR’s effects on human systemic immune function are not well understood. Several lines of evidence suggest that UVR may have immunosuppressive effects, however, no epidemiologic studies have investigated the association between quantitative measures of UVR and a biomarker of immune function. Objective: To evaluate the association between UVR and systemic immune function, we conducted a cross-sectional analysis of recent UVR and circulating regulatory T- cells (“Tregs”) among a cohort of skin cancer screening patients. Methods: 350 patients undergoing regular skin cancer screenings with no prevalent skin cancer at the time of enrollment were recruited from the University of South Florida Dermatology clinic. At the baseline visit, blood was obtained, and a spectrophotometer was used to measure skin pigmentation at a sun-unexposed site (the axilla) and two sun-exposed sites: the forehead and the upper forearm. Recent sun exposure was quantified as the difference in readings between the sun-exposed and sun-unexposed sites. Using flow cytometry assays, lymphocyte samples were examined for Tregs (CD4+CD25+ CD127lowFoxp3+), and proportions of Tregs with enhanced immunosuppressive function (CD27-, CD45RA- Treg) and skin tissue affinity (CLA+, CCR4high) were determined. Associations between UVR exposure and Tregs were described using Spearman correlation coefficients. Linear regression using log-transformed values of UVR and Tregs was used to adjust for age and sex. Results: Among all 350 participants, UVR was positively correlated with circulating immunosuppressive CD27-, CD45RA- Tregs (r=0.127, p=0.020 for UVR measured at the forehead and r=0.197, p=0.0002 for UVR measured at the forearm). UVR measured at the forearm was also positively correlated with skin-homing Tregs expressing CLA (r=0.167, p=0.002) and CCR4 (r=0.19, p=0.0004). When participants were categorized into light versus dark constitutive pigmentation based on the median value of spectrophotometer readings for the sun-unexposed axilla, the correlation between UVR averaged across the forehead and forearm was more strongly correlated with immunosuppressive Tregs among lighter-skin participants (r=0.30, p<0.001) than darker-skin participants (r=0.065, p=0.400). Conclusion: Recent UVR is positively associated with increased levels of circulating immunosuppressive Tregs, including Tregs with skin tissue affinity, with the association being stronger among naturally lighter-skinned individuals. UVR-associated immunosuppressive effects among otherwise immunocompetent individuals may play a role in skin cancer carcinogenesis. Citation Format: Dana E. Rollison, Shalaka S. Hampras, Jane L. Messina, Neil A. Fenske, Basil S. Cherpelis, Michael J. Schell, Rhianna Reed, Juliana Balliu, Rebecca Hesterberg, Afua A. Akuffo, Pearlie K. Burnette. Recent ultraviolet radiation exposure and circulating immunosuppressive T-regulatory cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4960. doi:10.1158/1538-7445.AM2017-4960