Cancer-Testis Antigens and Immunosurveillance in Human Cutaneous Squamous Cell and Basal Cell Carcinomas
Cancer-Testis Antigens and Immunosurveillance in Human Cutaneous Squamous Cell and Basal Cell Carcinomas
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DOI：
10.1158/1078-0432.ccr-09-3136
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发表时间：
2010-07-15
影响因子：
11.5
通讯作者：
van den Broek, Maries
中科院分区：
文献类型：
--
作者：
Walter, Anne;Barysch, Marjam J.;van den Broek, Maries
目的：非黑色素瘤皮肤癌是最常见的癌症，包括基底细胞癌（BCC）和鳞状细胞癌（SCC）。在免疫抑制个体中，鳞状细胞癌的发病率急剧增加，表明免疫系统在控制鳞状细胞癌中发挥着关键作用。为了找到 SCC 选择性免疫监视的解释，我们研究了 BCC 和 SCC 中癌症睾丸 (CT) 抗原和 MHC I 类 (MHC-I) 的表达以及免疫细胞的浸润。实验设计：我们确定了 63 个 BCC 和 40 个免疫功能正常的 SCC 活检组织以及 20 个免疫抑制的活检组织中 23 种不同 CT 抗原的表达。 通过逆转录 PCR 和免疫组织化学对 SCC 患者进行检测。通过蛋白质印迹和 ELISA 测量 IgG 对 36 种肿瘤抗原的反应。通过免疫组织化学分析免疫功能正常和免疫抑制患者的 BCC 和 SCC 以及接受咪喹莫特治疗的 BCC 患者中 MHC-I 表达和 CD8(+) T 细胞浸润。结果：我们发现 81% 的 BCC 和 40% 的 SCC 中至少有一种 CT 抗原表达。我们没有检测到 CT 抗原特异性血清 IgG。大多数鳞状细胞癌（但基底细胞癌除外）表达 MHC-I，并被 CD8+ 细胞浸润。咪喹莫特处理的 BCC 表达 MHC-I，并被 CD8+ T 细胞浸润。结论：我们认为免疫监视控制 SCC，但不能控制 BCC，因为后者缺乏 MHC-I。这与免疫抑制个体中鳞状细胞癌的发病率增加相符，并且可以解释由于 CD8+ T 细胞驱动的免疫编辑导致鳞状细胞癌中 CT 抗原表达的患病率相对较低。临床癌症研究； 16（14）； 3562-70。 (C) 2010 AACR。
Purpose: Nonmelanoma skin cancer is the most common cancer and comprises basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The incidence of SCC increases drastically in immunosuppressed individuals, suggesting a critical role of the immune system in controlling SCC. To find an explanation for the selective immunosurveillance of SCC, we investigated the expression of cancer-testis (CT) antigens and MHC class I (MHC-I) and the infiltration by immune cells in BCC and SCC.Experimental Design: We determined the expression of 23 different CT-antigens in 63 BCC and 40 SCC biopsies of immunocompetent and in 20 biopsies of immunosuppressed SCC patients by reverse transcription-PCR and immunohistochemistry. IgG responses to 36 tumor antigens were measured by Western blotting and ELISA. MHC-I expression and CD8(+) T-cell infiltration were analyzed by immunohistochemistry in BCC and SCC of immunocompetent and immunosuppressed patients and in imiquimod-treated BCC patients.Results: We found expression of at least one CT-antigen in 81% of BCC and in 40% of SCC. We did not detect CT-antigen-specific serum IgG. Most SCC, but not BCC, expressed MHC-I and were infiltrated with CD8+ cells. Imiquimod-treated BCC expressed MHC-I and were infiltrated by CD8+ T cells.Conclusions: We propose that immunosurveillance controls SCC, but not BCC, because the latter lacks MHC-I. This fits with the increased incidence of SCC in immunosuppressed individuals and may explain the relatively low prevalence of CT-antigen expression in SCC as a result of CD8+ T-cell-driven immunoediting. Clin Cancer Res; 16(14); 3562-70. (C) 2010 AACR.