Rollison Dana E, Messina Jane L, Cherpelis Basil S, Fenske Neil A, Schell Michael J, Adeegbe Dennis O, Zhao Yayi, Amorrortu Rossybelle P, Akuffo Afua A, Hesterberg Rebecca S, Epling-Burnette Pearlie K
Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, United States.
Departments of Pathology and Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, United States.
Front Med (Lausanne). 2021 Nov 2;8:735585. doi: 10.3389/fmed.2021.735585. eCollection 2021.
Ultraviolet radiation exposure (UVR) is a risk factor for cutaneous squamous cell carcinoma (cuSCC) and has been shown to be positively associated with circulating immunosuppressive regulatory T cells ("Tregs"). However, the risk of cuSCC in association with circulating Tregs has not been studied. The aim of this study was to determine whether circulating Treg levels are associated with cuSCC development, particularly in the context of high UVR. Blood and spectrophotometer-based UVR measurements were obtained on 327 immunocompetent individuals undergoing routine skin cancer screenings at baseline and followed for up to 4 years for incident cuSCC development within a prospective cohort study. Proportions of phenotypically distinct Tregs, especially CCR4 and CLA cells which are associated with activation and homing, respectively, were measured by flow cytometry. Tregs in cuSCC tumors were assessed using immunohistochemistry and graded for solar elastosis, a measure of cumulative UVR damage. Of several Treg phenotypes examined, higher levels of circulating CCR4 Tregs at baseline were significantly associated with increased risk of subsequent cuSCC; those with higher levels of both CCR4 and UVR were four times more likely to develop cuSCC compared to those with lower levels of both (Hazard Ratio = 4.11, 95% CI = 1.22-13.90). Within cuSCC tumors, CCR4 Tregs were positively associated with solar elastosis. Results show that a higher proportion of CCR4 peripheral Tregs predicts incident cuSCC up to 4 years, especially among highly UV-exposed individuals. Research of the underpinning biology of Tregs in UVR-associated skin damage may possibly reveal novel opportunities for screening, prevention, and treatment.
紫外线辐射暴露（UVR）是皮肤鳞状细胞癌（cuSCC）的一个风险因素，并且已被证明与循环免疫抑制调节性T细胞（“Tregs”）呈正相关。然而，与循环Tregs相关的cuSCC风险尚未得到研究。本研究的目的是确定循环Treg水平是否与cuSCC的发生有关，特别是在高UVR的情况下。在前瞻性队列研究中，对327名接受常规皮肤癌筛查的免疫功能正常个体在基线时进行了血液和基于分光光度计的UVR测量，并随访长达4年以观察cuSCC的发生情况。通过流式细胞术测量表型不同的Tregs的比例，特别是分别与激活和归巢相关的CCR4和CLA细胞。使用免疫组织化学评估cuSCC肿瘤中的Tregs，并对日光性弹力组织变性进行分级，这是一种累积UVR损伤的测量方法。在所检查的几种Treg表型中，基线时循环CCR4 Tregs水平较高与随后发生cuSCC的风险增加显著相关；与两者水平较低的个体相比，CCR4和UVR水平都较高的个体发生cuSCC的可能性高出四倍（风险比 = 4.11，95%置信区间 = 1.22 - 13.90）。在cuSCC肿瘤中，CCR4 Tregs与日光性弹力组织变性呈正相关。结果表明，较高比例的CCR4外周Tregs可预测长达4年的cuSCC发生情况，特别是在高紫外线暴露个体中。对UVR相关皮肤损伤中Tregs的基础生物学研究可能会揭示筛查、预防和治疗的新机会。
