Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target
Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target
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DOI：
10.1073/pnas.0406351101
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发表时间：
2004-12-07
影响因子：
11.1
通讯作者：
Kwon, ED
中科院分区：
文献类型：
--
作者：
Thompson, RH;Gillettt, MD;Kwon, ED
B7-H1是B7家族中的一种共刺激糖蛋白，其表达通常局限于巨噬细胞系细胞，为调节T细胞激活提供了潜在的共刺激信号源。相反，肿瘤细胞B7-H1的异常表达与T细胞功能和存活的损害有关，从而导致宿主抗肿瘤免疫缺陷。肿瘤相关的B7-H1与临床肿瘤进展的关系尚不清楚。在此，我们报告了B7-H1在肾细胞癌(RCC)肿瘤和肾细胞癌肿瘤浸润性淋巴细胞中的表达。此外，我们对196个临床标本的分析显示，肿瘤内B7-H1高表达的患者，单独由肿瘤细胞、单独淋巴细胞或肿瘤和/或淋巴细胞联合作用，表现出侵袭性肿瘤，并显著增加死于肾癌的风险。事实上，肿瘤和/或淋巴细胞B7-H1水平高的患者死于癌症的可能性是B7-H1低水平患者的4.5%(风险比4.53；95%可信区间1.94-10.56；P<；0.001)。因此，我们的研究提出了一种以前未被描述的机制，即肾细胞癌可能损害宿主免疫以促进肿瘤进展。B7-H1可作为肾癌患者治疗前和治疗后的一个有用的预后变量。此外，对于需要免疫治疗的晚期肾癌患者，B7-H1可能是一个有希望的靶点，以促进更有利的反应。
Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to macrophage-lineage cells, providing a potential costimulatory signal source for regulation of T cell activation. In contrast, aberrant expression of B7-H1 by tumor cells has been implicated in impairment of T cell function and survival, resulting in defective host antitumoral immunity. The relationship between tumor-associated B7-H1 and clinical cancer progression is unknown. Herein, we report B7-H1 expression by both renal cell carcinoma (RCC) tumors of the kidney and RCC tumor-infiltrating lymphocytes. In addition, our analysis of 196 clinical specimens reveals that patients harboring high intratumoral expression levels of B7-H1, contributed by tumor cells alone, lymphocytes alone, or tumor and/or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and/or lymphocyte B7-H1 levels are 4.5 times more likely to die from their cancer than patients exhibiting low levels of B7-H1 expression (risk ratio 4.53; 95% confidence interval 1.94-10.56; P < 0.001.) Thus, our study suggests a previously undescribed mechanism whereby RCC may impair host immunity to foster tumor progression. B7-H1 may prove useful as a prognostic variable for RCC patients both pre- and posttreatment. In addition, B7-H1 may represent a promising target to facilitate more favorable responses in patients who require immunotherapy for treatment of advanced RCC.