文章：

肿瘤环境中的免疫抑制网络及其治疗相关性

Immunosuppressive networks in the tumour environment and their therapeutic relevance

原文发布日期：2005-03-18

DOI: 10.1038/nrc1586

类型: Review Article

开放获取: 否

要点：

1. The pathological interactions between cancer cells and host immune cells in the tumour microenvironment create an immunosuppressive network that promotes tumour growth, protects the tumour from immune attack and attenuates immunotherapeutic efficacy.
2. Poor tumour-associated antigen (TAA)-specific immunity is not simply due to a passive process whereby adaptive immunity is shielded from detecting TAAs. There is an active process of 'tolerization' taking place in the tumour microenvironment.
3. Tumour tolerization is the result of imbalances in the tumour microenvironment, including alterations in antigen-presenting-cell subsets, co-stimulatory and co-inhibitory molecule alterations and altered ratios of effector T cells and regulatory T cells.
4. Human tumorigenesis is a slow process that can occur over several years and in this respect is similar to chronic infection. The lack of an acute phase in the course of tumorigenesis might profoundly shape T-cell immune responses, including the quality of antigen release, T-cell priming and activation.
5. Current immunotherapies often target patients with advanced-stage tumours, which have high levels of inflammatory molecules, cytokines, chemokines, tumour-infiltrating T cells, dendritic cells and macrophages. It is arguable whether we need to incorporate more of these components into tumour treatments.
6. Immune tolerization is predominant in the immune system in patients with advanced-stage tumours. It is time to consider combinatorial tumour therapies, including those that subvert the immune-tolerizing conditions within the tumour.

要点翻译：

1. 肿瘤微环境中癌细胞与宿主免疫细胞之间的病理相互作用，构建了一个免疫抑制网络——该网络不仅促进肿瘤生长、保护肿瘤免受免疫攻击，还会削弱免疫治疗效果。
2. 肿瘤相关抗原（TAA）特异性免疫应答低下并非单纯因为适应性免疫无法识别TAA的被动过程，而是肿瘤微环境中持续发生的主动"耐受化"过程。
3. 肿瘤耐受化是肿瘤微环境失衡的结果，包括抗原呈递细胞亚群改变、共刺激与共抑制分子变化，以及效应T细胞与调节性T细胞比例失调。
4. 人类肿瘤发生是一个可长达数年的缓慢过程，这方面与慢性感染相似。肿瘤发生过程中急性炎症阶段的缺失可能深刻影响T细胞免疫应答，包括抗原释放质量、T细胞启动与激活等特性。
5. 当前免疫疗法常以晚期肿瘤患者为对象，这些患者的肿瘤微环境富含炎症分子、细胞因子、趋化因子、肿瘤浸润T细胞、树突状细胞和巨噬细胞。是否需要将更多此类成分纳入肿瘤治疗尚存争议。
6. 晚期肿瘤患者的免疫系统中，免疫耐受占据主导地位。当前亟需考虑联合治疗方案，包括那些能够逆转肿瘤内免疫耐受状态的策略。

英文摘要：

It is well known that many tumours are potentially immunogenic, as corroborated by the presence of tumour-specific immune responses in vivo. Nonetheless, spontaneous clearance of established tumours by endogenous immune mechanisms is rare. Therefore, the focus of most cancer immunotherapies is to supplement essential immunogenic elements to boost tumour-specific immunity. Why then has tumour immunotherapy resulted in a generally poor clinical efficiency? The reason might lie in the increasingly documented fact that tumours develop diverse strategies that escape tumour-specific immunity.

摘要翻译： 

众所周知，许多肿瘤具有潜在的免疫原性，体内存在的肿瘤特异性免疫反应可证实这一点。然而，由机体内源性免疫机制自发清除已形成的肿瘤极为罕见。因此，大多数肿瘤免疫疗法的核心在于补充关键的免疫原性成分，以增强针对肿瘤的特异性免疫反应。那么，为何肿瘤免疫治疗的临床疗效普遍不佳？原因可能在于一个日益被证实的事实：肿瘤会发展出多种策略，以逃避肿瘤特异性免疫的清除。

原文链接：

Immunosuppressive networks in the tumour environment and their therapeutic relevance