Tumor Cell Expression of Programmed Cell Death-1 Ligand 1 Is a Prognostic Factor for Malignant Melanoma
Tumor Cell Expression of Programmed Cell Death-1 Ligand 1 Is a Prognostic Factor for Malignant Melanoma
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DOI：
10.1002/cncr.24899
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发表时间：
2010-04-01
期刊：
影响因子：
6.2
通讯作者：
Tokura, Yoshiki
中科院分区：
文献类型：
--
作者：
Hino, Ryosuke;Kabashima, Kenji;Tokura, Yoshiki
背景：由于肿瘤诱导的免疫抑制，黑色素瘤往往对各种免疫疗法难以治疗。为了研究黑色素瘤患者免疫抑制的机制，作者专注于肿瘤细胞和T细胞之间的程序性细胞死亡-1（PD-1）/PD-1配体1（PD-L1）相互作用。方法：从59例原发肿瘤、16个淋巴结和4个转移灶中收集黑色素瘤标本。将抗PD-L1单克隆抗体染色的标本数字化为jpg文件。为了评价PD-L1表达的强度，使用直方图，并测量红色密度（RD）。在来自10名患有IV期黑色素瘤的患者的血液样品和4个在途转移的样品中分析了T细胞上的PD-1表达。结果：25例患者组成“低”PD-L1表达组（RD值= 90）。高表达组Breslow肿瘤厚度明显高于低表达组。单因素和多因素分析显示，高表达组的总生存率显著低于低表达组。在所有接受检查的IV期疾病患者中，CD 8阳性和CD 4阳性T细胞在外周血中的PD-1表达水平均显著较高。肿瘤浸润性T细胞表达高水平的PD-1，并且其表达在临床过程中进一步升高。结论：目前的结果表明，PD-L1表达程度与黑色素瘤原发肿瘤的垂直生长之间存在相关性。多因素分析表明PD-L1表达是黑色素瘤的独立预后因素。Cancer 2010;116：1757-66. (C)2010年美国癌症协会
BACKGROUND: Melanoma tends to be refractory to various immunotherapies because of tumor-induced immunosuppression. To investigate the mechanism underlining the immunosuppression of melanoma patients, the authors focused on programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) interaction between tumor cells and T cells. METHODS: Melanoma specimens were collected from 59 primary tumors, 16 lymph nodes, and 4 lesions of in-transit metastasis. Specimens stained with anti-PD-L1 monoclonal antibodies were digitalized to jpg files. To evaluate the intensity of PD-L1 expression, histograms were used, and the red density (RD) was measured. PD-1 expression on T cells was analyzed in blood samples from 10 patients who had stage IV melanoma and in 4 samples of in-transit metastases. RESULTS: Twenty-five patients comprised the "low" PD-L1 expression group (RD value, = 90). Breslow tumor thickness in the high-expression group was significantly higher than in the low-expression group. Univariate and multivariate analyses revealed that the overall survival rate of the high-expression group was significantly lower than that of the low-expression group. In all patients with stage IV disease who were examined, both CD8-positive and CD4-positive T cells had significantly higher PD-1 expression levels in the peripheral blood. Tumor-infiltrating T cells expressed high levels of PD-1, and its expression was elevated further during the clinical course. CONCLUSIONS: The current results indicated that there is a correlation between the degree of PD-L1 expression and the vertical growth of primary tumors in melanoma. Multivariate analysis demonstrated that PD-L1 expression is an independent prognostic factor for melanoma. Cancer 2010;116:1757-66. (C) 2010 American Cancer Society