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利用先天免疫和适应性免疫进行肾细胞癌的过继性细胞治疗。

Harnessing innate and adaptive immunity for adoptive cell therapy of renal cell carcinoma.

作者信息

Geiger Christiane, Nössner Elfriede, Frankenberger Bernhard, Falk Christine S, Pohla Heike, Schendel Dolores J

机构信息

Institut für Molekulare Immunologie, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Germany.

出版信息

J Mol Med (Berl). 2009 Jun;87(6):595-612. doi: 10.1007/s00109-009-0455-2. Epub 2009 Mar 7.

Abstract

The development of immunotherapies for renal cell carcinoma (RCC) has been the subject of research for several decades. In addition to cytokine therapy, the benefit of various adoptive cell therapies has again come into focus in the past several years. Nevertheless, success in fighting this immunogenic tumor is still disappointing. RCC can attract a multitude of different effector cells of both the innate and adaptive immune system, including natural killer (NK) cells, gammadelta T cells, NK-like T cells, peptide-specific T cells, dendritic cells (DC), and regulatory T cells (Tregs). Based on intensive research on the biology and function of different immune cells, we now understand that individual cell types do not act in isolation but function within a complex network of intercellular interactions. These interactions play a pivotal role in the efficient activation and function of effector cells, which is a prerequisite for successful tumor elimination. This review provides a current overview of the diversity of effector cells having the capacity to recognize RCC. Aspects of the functions and anti-tumor properties that make them attractive candidates for adoptive cell therapies, as well as experience in clinical application are discussed. Improved knowledge of the biology of this immune network may help us to effectively harness various effector cells, placing us in a better position to develop new therapeutic strategies to successfully fight RCC.

摘要

几十年来,肾细胞癌(RCC)免疫疗法的开发一直是研究的主题。除了细胞因子疗法外,各种过继性细胞疗法的益处近年来再次成为焦点。然而,对抗这种免疫原性肿瘤的成效仍然令人失望。肾细胞癌能够吸引先天性和适应性免疫系统的多种不同效应细胞,包括自然杀伤(NK)细胞、γδT细胞、NK样T细胞、肽特异性T细胞、树突状细胞(DC)和调节性T细胞(Tregs)。基于对不同免疫细胞生物学和功能的深入研究,我们现在明白,单个细胞类型并非孤立发挥作用,而是在细胞间相互作用的复杂网络中发挥功能。这些相互作用在效应细胞的有效激活和功能发挥中起着关键作用,而这是成功消除肿瘤的先决条件。本综述提供了目前对具有识别肾细胞癌能力的效应细胞多样性的概述。讨论了使其成为过继性细胞疗法有吸引力候选者的功能和抗肿瘤特性方面,以及临床应用经验。对这种免疫网络生物学的深入了解可能有助于我们有效利用各种效应细胞,使我们更有能力开发成功对抗肾细胞癌的新治疗策略。

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