文章：

内质网应激在抗癌免疫中的作用

Endoplasmic reticulum stress responses in anticancer immunity

原文发布日期：2025-06-24

DOI: 10.1038/s41568-025-00836-5

类型: Review Article

开放获取: 否

英文摘要：

The endoplasmic reticulum (ER) has a central role in processes essential for mounting effective and durable antitumour immunity; this includes regulating protein synthesis, folding, modification and trafficking in immune cells. However, the tumour microenvironment imposes hostile conditions that disrupt ER homeostasis in both malignant and infiltrating immune cells, leading to chronic activation of the unfolded protein response (UPR). Dysregulated ER stress responses have emerged as critical modulators of cancer progression and immune escape, influencing the initiation, development and maintenance of antitumour immunity. In this Review, we examine how tumour-induced ER stress reshapes the functional landscape of immune cells within the tumour microenvironment. We highlight recent discoveries demonstrating how ER stress curtails endogenous antitumour immunity and reduces the efficacy of immunotherapies. Furthermore, we underscore novel therapeutic strategies targeting ER stress sensors or UPR components to restore immune function and enhance cancer immunotherapy outcomes. Together, this provides a comprehensive overview of the interplay between ER stress responses and antitumour immunity, emphasizing the potential of UPR-targeted interventions to improve immune control of cancer.

摘要翻译： 

内质网在产生有效且持久的抗肿瘤免疫过程中起着核心作用，包括调控免疫细胞中的蛋白质合成、折叠、修饰和运输。然而，肿瘤微环境所呈现的恶劣条件会破坏恶性细胞和浸润免疫细胞的内质网稳态，导致未折叠蛋白反应长期激活。内质网应激反应的失调已成为癌症进展和免疫逃逸的关键调节因素，影响着抗肿瘤免疫的启动、发展和维持。本篇综述中，我们探讨了肿瘤诱导的内质网应激如何重塑肿瘤微环境中免疫细胞的功能格局。我们重点介绍了最新发现，阐明内质网应激如何抑制内源性抗肿瘤免疫并降低免疫疗法的疗效。此外，我们强调针对内质网应激感应器或未折叠蛋白反应组分的新型治疗策略，以恢复免疫功能并提升癌症免疫治疗效果。本文全面概述了内质网应激反应与抗肿瘤免疫之间的相互作用，强调了靶向未折叠蛋白反应的干预措施在改善癌症免疫控制方面的潜力。

原文链接：

Endoplasmic reticulum stress responses in anticancer immunity