Yesantharao Pooja, Wang Wei, Ioannidis Nilah M, Demehri Shadmehr, Whittemore Alice S, Asgari Maryam M
Epidemiology Division, Department of Health Research & Policy, Stanford University, Stanford, CA 94305, USA.
Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Hum Immunol. 2017 Apr;78(4):327-335. doi: 10.1016/j.humimm.2017.02.002. Epub 2017 Feb 7.
Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer among Caucasians in the United States, with rising incidence over the past decade. Treatment for non-melanoma skin cancer, including cSCC, in the United States was estimated to cost $4.8 billion in 2014. Thus, an understanding of cSCC pathogenesis could have important public health implications. Immune function impacts cSCC risk, given that cSCC incidence rates are substantially higher in patients with compromised immune systems. We report a systematic review of published associations between cSCC risk and the human leukocyte antigen (HLA) system. This review includes studies that analyze germline class I and class II HLA allelic variation as well as HLA cell-surface protein expression levels associated with cSCC risk. We propose biological mechanisms for these HLA-cSCC associations based on known mechanisms of HLA involvement in other diseases. The review suggests that immunity regulates the development of cSCC and that HLA-cSCC associations differ between immunocompetent and immunosuppressed patients. This difference may reflect the presence of viral co-factors that affect tumorigenesis in immunosuppressed patients. Finally, we highlight limitations in the literature on HLA-cSCC associations, and suggest directions for future research aimed at understanding, preventing and treating cSCC.
皮肤鳞状细胞癌（cSCC）是美国白种人中第二常见的癌症，在过去十年中发病率呈上升趋势。2014年，美国包括cSCC在内的非黑色素瘤皮肤癌的治疗费用估计为48亿美元。因此，了解cSCC的发病机制可能具有重要的公共卫生意义。鉴于免疫系统受损患者的cSCC发病率显著更高，免疫功能会影响cSCC风险。我们报告了一项关于已发表的cSCC风险与人类白细胞抗原（HLA）系统之间关联的系统综述。该综述包括分析I类和II类HLA种系等位基因变异以及与cSCC风险相关的HLA细胞表面蛋白表达水平的研究。我们基于HLA参与其他疾病的已知机制，提出了这些HLA与cSCC关联的生物学机制。该综述表明，免疫调节cSCC的发生发展，且HLA与cSCC的关联在免疫功能正常和免疫抑制患者之间存在差异。这种差异可能反映了影响免疫抑制患者肿瘤发生的病毒辅助因子的存在。最后，我们强调了关于HLA与cSCC关联的文献中的局限性，并提出了未来旨在了解、预防和治疗cSCC的研究方向。
