Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan.
Cancer. 2010 Apr 1;116(7):1757-66. doi: 10.1002/cncr.24899.
: 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.
: 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.
: Twenty-five patients comprised the "low" PD-L1 expression group (RD value, <90), and 34 patients comprised the "high" group (RD value, > or =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.
: 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. (c) 2010 American Cancer Society.
黑色素瘤由于肿瘤诱导的免疫抑制而对各种免疫疗法具有抗性。为了研究导致黑色素瘤患者免疫抑制的机制，作者们专注于肿瘤细胞和 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。
从 59 个原发性肿瘤、16 个淋巴结和 4 个转移病灶中收集黑色素瘤标本。用抗 PD-L1 单克隆抗体对标本进行染色，然后将其数字化为 jpg 文件。为了评估 PD-L1 表达的强度，使用了直方图，并测量了红色密度（RD）。对 10 名患有 IV 期黑色素瘤的患者和 4 份转移病灶样本的血液样本中的 T 细胞上的 PD-1 表达进行了分析。
25 名患者组成“低”PD-L1 表达组（RD 值<90），34 名患者组成“高”组（RD 值≥90）。高表达组的 Breslow 肿瘤厚度明显高于低表达组。单因素和多因素分析表明，高表达组的总生存率明显低于低表达组。在所有接受检查的 IV 期疾病患者中，外周血中 CD8 阳性和 CD4 阳性 T 细胞的 PD-1 表达水平均显著升高。肿瘤浸润 T 细胞表达高水平的 PD-1，并且在临床过程中其表达进一步升高。
目前的结果表明，黑色素瘤中 PD-L1 表达程度与原发性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。癌症 2010。（c）2010 年美国癌症协会。
