Unraveling UPR-mediated intercellular crosstalk: Implications for immunotherapy resistance mechanisms

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2025-03-05 DOI:10.1016/j.canlet.2025.217613

Si Lu , Qimin Zhou , Rongjie Zhao , Lei Xie , Wen-Ming Cao , Yu-Xiong Feng

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引用次数: 0

Abstract

Endoplasmic reticulum (ER) is the critical organelle that regulates essential cellular processes, including protein synthesis, folding, and post-translational modification, as well as lipid metabolism and calcium homeostasis. Disruption in ER homeostasis leads to a condition known as ER stress, characterized by the accumulation of misfolded or unfolded proteins. This triggers the unfolded protein response (UPR), an adaptive pathway mediated by three ER-resident sensors: inositol-requiring enzyme 1α (IRE1α), protein kinase R-like ER kinase (PERK), and activating transcription factor 6 (ATF6). Increasing evidence highlights sustained UPR activation in malignant and immune cells within the tumor microenvironment (TME), which promotes tumor progression and metastasis while simultaneously impairing antitumor immunity. This review explores how UPR-driven intercellular signaling influences immunotherapy resistance, focusing on the alterations occurring in tumor cells as well as in the surrounding immune environment. By providing insights into these mechanisms, we aim to highlight the therapeutic potential of targeting the UPR pathways in modulating cancer immunity.

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揭示upr介导的细胞间串扰：对免疫治疗耐药机制的影响。

内质网（ER）是调节重要细胞过程的关键细胞器，包括蛋白质合成、折叠和翻译后修饰，以及脂质代谢和钙稳态。内质网稳态的破坏导致内质网应激，其特征是错误折叠或未折叠蛋白质的积累。这触发了未折叠蛋白反应（UPR），这是一种由三个内质网驻留传感器介导的适应性途径：肌醇要求酶1α (IRE1α)、蛋白激酶r样内质网激酶（PERK）和激活转录因子6 （ATF6）。越来越多的证据表明，肿瘤微环境（TME）中的恶性和免疫细胞中持续的UPR激活促进了肿瘤的进展和转移，同时损害了抗肿瘤免疫。这篇综述探讨了upr驱动的细胞间信号传导如何影响免疫治疗耐药性，重点关注肿瘤细胞以及周围免疫环境中发生的改变。通过深入了解这些机制，我们的目标是强调靶向UPR通路调节癌症免疫的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.