皮肤鳞状细胞癌患者中针对p53的CD8 + T细胞反应。
p53-specific CD8+ T-cell responses in individuals with cutaneous squamous cell carcinoma.
作者信息
Black A P, Bailey A, Jones L, Turner R J, Hollowood K, Ogg G S
机构信息
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
出版信息
Br J Dermatol. 2005 Nov;153(5):987-91. doi: 10.1111/j.1365-2133.2005.06878.x.
BACKGROUND
Systemic immunosuppression is a significant risk factor for cutaneous squamous cell carcinoma (SCC). p53 is mutated and overexpressed in up to 90% of cutaneous SCC lesions. Despite considerable evidence that the immune response is important in the control of cutaneous SCC, there are no studies documenting potential tumour-associated antigens.
OBJECTIVES
We tested the hypothesis that individuals with cutaneous SCC have functional circulating CD8+ T cells specific for p53.
METHODS
Interferon-gamma immunosorbent assays were used to screen peripheral blood mononuclear cells for reactivity to six p53-derived HLA-A0201-restricted epitopes from HLA-A0201-positive patients and controls.
RESULTS
We observed significantly elevated frequencies of p53-specific CD8+ T cells in seven of 26 individuals with cutaneous SCC and in one of 10 controls. The degree of lymphocytic infiltrate significantly correlated with the frequency of CD8+ T cells specific for p53 epitopes, but not with control epitopes.
CONCLUSIONS
Overall, these data suggest that p53 may represent a target for CD8+ T cells in a proportion of individuals with cutaneous SCC.
背景
全身免疫抑制是皮肤鳞状细胞癌（SCC）的一个重要危险因素。在高达90%的皮肤SCC病变中，p53发生突变并过表达。尽管有大量证据表明免疫反应在皮肤SCC的控制中很重要，但尚无研究记录潜在的肿瘤相关抗原。
目的
我们检验了以下假设，即皮肤SCC患者具有针对p53的功能性循环CD8+T细胞。
方法
使用干扰素-γ免疫吸附试验筛选外周血单核细胞对来自HLA-A0201阳性患者和对照的六个p53衍生的HLA-A0201限制性表位的反应性。
结果
我们观察到，在26例皮肤SCC患者中的7例以及10例对照中的1例中，p53特异性CD8+T细胞的频率显著升高。淋巴细胞浸润程度与p53表位特异性CD8+T细胞的频率显著相关，但与对照表位无关。
结论
总体而言，这些数据表明，在一部分皮肤SCC患者中，p53可能是CD8+T细胞的一个靶点。
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