Heat shock proteins in renal cell carcinomas
Heat shock proteins in renal cell carcinomas
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DOI：
10.1159/000086042
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发表时间：
2005-01-01
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影响因子：
--
通讯作者：
Seliger, B
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文献类型：
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作者：
Atkins, D;Lichtenfels, R;Seliger, B
肾细胞癌（RCC）是西方世界最常见的癌症类型之一。三分之一的RCC患者在就诊时有转移，5年生存率很低。肾切除术是最重要的治疗方式，这种疾病，因为大多数RCC是耐细胞毒化疗和放射治疗。最近的免疫治疗方法已被证明可以提高RCC患者的生存率。因此，RCC似乎具有免疫原性基础，因此代表了免疫疗法的有吸引力的靶标。到目前为止，只有少数RCC相关抗原的特点。然而，随着基于“ome”的技术的实施，已经鉴定了越来越多的肿瘤相关抗原和肿瘤标志物，包括各种热休克蛋白（HSP）。肾细胞癌病变表现出热休克蛋白的异质性表达模式。在大多数情况下，与正常肾上皮相比，在RCC细胞系以及肿瘤病变中检测到某些HSP（如HSP 27、HSP 70和HSP 72）的过表达。此外，热休克蛋白在细胞凋亡，细胞增殖的调节，并在增强溶细胞RCC的HLA I类限制性细胞毒性T淋巴细胞中发挥重要作用。在这种情况下，值得注意的是，野生型和突变的HSP已被确定为肿瘤相关抗原，从而导致第一个临床I期和11个试验使用HSP接种RCC患者。在本章中，我们将简要介绍热休克蛋白在肾细胞癌的病理机制的相关性。版权所有（c）2005 S. Karger AG，巴塞尔。
Renal cell carcinoma (RCC) represents one of the most common cancer types in the Western World. One third of the RCC patients had metastasis at presentation with a poor 5-year survival. Nephrectomy is the most important treatment modality of this disease, since most of the RCCs are resistant to cytotoxic chemotherapy and radiation therapy. Recent immunotherapeutic approaches have been shown to improve the survival rate of RCC patients. Thus, RCC appears to have an immunogenic basis, and therefore represents an attractive target for immunotherapies. So far, only a few RCC-associated antigens have been characterized. However, with the implementation of 'ome'-based technologies, an increasing number of tumor-associated antigens and tumor markers has been identified that includes various heat shock proteins (HSPs). RCC lesions demonstrate heterogeneous expression patterns for HSPs. In most cases overexpression of certain HSPs, such as HSP27, HSP70 and HSP72, has been detected both in RCC cell lines as well as in the tumor lesions when compared to normal kidney epithelium. Furthermore, HSPs play an important role in apoptotic cell death, in the regulation of cell proliferation and in the augmentation of lysis of RCC by HLA class I-restricted cytotoxic T lymphocytes. In this context, it is noteworthy that wild-type and mutated HSPs have been identified to act as tumor-associated antigens, which consequently resulted in the first clinical phase I and 11 trials using HSP for vaccination of RCC patients. In this chapter we will briefly present the relevance of HSPs in the pathomechanisms of RCC. Copyright (c) 2005 S. Karger AG, Basel.