Dynamic changes of specific T cell responses to melanoma correlate with IL-2 administration
Dynamic changes of specific T cell responses to melanoma correlate with IL-2 administration
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DOI：
10.1016/j.semcancer.2003.09.009
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发表时间：
2003-12-01
影响因子：
14.5
通讯作者：
Straten, PT
中科院分区：
文献类型：
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作者：
Andersen, MH;Gehl, J;Straten, PT
白细胞介素2（IL-2）是一种很有前途的免疫调节剂，用于治疗转移性黑色素瘤和肾癌。高剂量IL-2的全身给药在高达25%的黑素瘤患者中产生客观反应，并且这些患者中的低但显著比例经历持久反应。然而，在IL-2治疗过程中负责诱导肿瘤消退的细胞和分子仍然未知。肿瘤免疫治疗的新策略在过去十年中已经发展，这是该领域取得重大进展的结果。特别是关于来源于肿瘤相关抗原的肽表位的表征，以及抗原呈递细胞在细胞免疫应答起始中的作用。伴随着这些事实和概念上的进步。已经开发了新的方法来监测和表征癌症患者中的抗肿瘤T细胞应答。应用这些工具来剖析抗肿瘤应答已经证明，各种免疫治疗方法可以诱导强大的全身性抗肿瘤细胞毒性T淋巴细胞（CTL）应答。然而，使用当今工具来分析接受基于IL-2的免疫疗法治疗的患者的抗肿瘤免疫反应的努力有限。我们已经检查了在基于IL-2的免疫疗法（电化学疗法）的过程中黑素瘤患者中针对已知肿瘤抗原的CTL应答。令人惊讶的是，抗肿瘤CTL应答在治疗开始时显著下降，但当IL-2给药暂停时又出现。对应答T细胞的克隆型组成的分子分析表明，在治疗过程中出现了新的克隆，并且随后可以在肿瘤部位检测到离开外周血的肿瘤特异性T细胞。这些数据为IL-2的生物学作用提供了新的见解，并突出了与监测抗肿瘤免疫反应相关的困难。这强调了频繁采样血液和肿瘤活检的重要性，以结合最先进的技术进行分析，以获得关于癌细胞和免疫系统细胞之间相互作用的详细信息。(C)2003爱思唯尔有限公司。保留所有权利。
Interleukin 2 (IL-2) is a promising immunotherapeutic agent for the treatment of metastatic melanoma and renal cell carcinoma. Systemic administration of high dose IL-2 produces objective responses in up to 25% of melanoma patients, and a low but significant proportion of these patients experience durable responses. Nevertheless, the cells and molecules responsible for induction of tumor regression over the course of IL-2 treatment remain unknown. New strategies in tumor immunotherapy have evolved over the past decade as a consequence of significant progress in the field. in particular with respect to the characterization of peptide epitopes derived from tumor associated antigens, and the role of antigen presenting cells in the initiation of cellular immune responses. Alongside with these factual as well as conceptual advances. new methods have been developed to monitor and characterize anti-tumor T cell responses in cancer patients. Application of these tools to dissect anti-tumor responses has demonstrated that various immune therapeutic approaches can induce powerful systemic anti-tumor cytotoxic T lymphocyte (CTL) responses. However, only limited efforts have been made to use present days tool to analyze anti-tumor immune responses in patients treated with IL-2 based immunotherapy. We have examined CTL responses against known tumor antigens in melanoma patients over the course of IL-2 based immunotherapy (electrochemotherapy). Surprisingly, anti-tumor CTL responses significantly declined upon initiation of therapy, but reappeared when IL-2 administration was paused. Molecular analyses of the clonotypic composition of responding T cells demonstrated that new clones emerged over the course of treatment, and that tumor-specific T cells that had left the peripheral blood could subsequently be detected at the tumor site. These data provide new insight into the biological actions of IL-2 and highlight the difficulties associated with the monitoring of anti-tumor immune responses. This underlines the importance of frequent sampling of blood and tumor biopsies to be analyzed with a combination of state of the art technologies in order to gain detailed information on the interactions between cancer cells and cells of the immune system. (C) 2003 Elsevier Ltd. All rights reserved.