The tumour microenvironment (TME) highly influences the growth and spread of tumours, thus impacting the patient's clinical outcome. In this context, the complement system plays a major and complex role. It may either act to kill antibody-coated tumour cells, support local chronic inflammation or hamper antitumour T cell responses favouring tumour progression. Recent studies demonstrate that these opposing effects are dependent upon the sites of complement activation, the composition of the TME and the tumour cell sensitivity to complement attack. In this Review, we present the evidence that has so far accrued showing a role for complement activation and its effects on cancer control and clinical outcome under different TME contexts. We also include a new analysis of the publicly available transcriptomic data to provide an overview of the prognostic value of complement gene expression in 30 cancer types. We argue that the interplay of complement components within each cancer type is unique, governed by the properties of the tumour cells and the TME. This concept is of critical importance for the design of efficient therapeutic strategies aimed at targeting complement components and their signalling.

中文翻译：

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补体在癌症中的上下文依赖性作用。

肿瘤微环境 (TME) 高度影响肿瘤的生长和扩散，从而影响患者的临床结果。在这种情况下，补体系统起着重要而复杂的作用。它可能起到杀死抗体包被的肿瘤细胞的作用，支持局部慢性炎症或阻碍有利于肿瘤进展的抗肿瘤 T 细胞反应。最近的研究表明，这些相反的作用取决于补体激活位点、TME 的组成和肿瘤细胞对补体攻击的敏感性。在这篇综述中，我们展示了迄今为止积累的证据，显示补体激活的作用及其在不同 TME 环境下对癌症控制和临床结果的影响。我们还包括对公开可用的转录组数据的新分析，以概述补体基因表达在 30 种癌症类型中的预后价值。我们认为，每种癌症类型中补体成分的相互作用是独一无二的，受肿瘤细胞和 TME 的特性支配。这一概念对于设计针对补体成分及其信号传导的有效治疗策略至关重要。