Bladder cancer (BC) is a common malignant tumor of the urinary system. While current approaches involving adjuvant chemotherapy, radiotherapy, and immunotherapy have shown significant progress in BC treatment, challenges, such as recurrence and drug resistance, persist, especially in the case of muscle-invasive bladder cancer (MIBC). It is mainly due to the lack of pre-existing immune response cells in the tumor immune microenvironment. Micro-environmental changes (such as hypoxia and under-nutrition) can cause the aggregation of unfolded and misfolded proteins in the lumen, which induces endoplasmic reticulum (ER) stress. ER stress and its downstream signaling pathways are closely related to immunogenicity and tumor drug resistance. ER stress plays a pivotal role in a spectrum of processes within immune cells and the progression of BC cells, encompassing cell proliferation, autophagy, apoptosis, and resistance to therapies. Recent studies have increasingly recognized the potential of natural compounds to exhibit anti-BC properties through ER stress induction. Still, the efficacy of these natural compounds remains less than that of immune checkpoint inhibitors (ICIs). Currently, the ER stress-mediated immunogenic cell death (ICD) pathway is more encouraging, which can enhance ICI responses by mediating immune stemness. This article provides an overview of the recent developments in understanding how ER stress influences tumor immunity and its implications for BC. Targeting this pathway may soon emerge as a compelling therapeutic strategy for BC.

中文翻译：

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膀胱癌内质网应激信号的免疫串扰

膀胱癌（BC）是泌尿系统常见的恶性肿瘤。虽然目前涉及辅助化疗、放疗和免疫疗法的方法在 BC 治疗方面取得了显着进展，但复发和耐药性等挑战仍然存在，特别是在肌层浸润性膀胱癌 (MIBC) 的情况下。这主要是由于肿瘤免疫微环境中缺乏预先存在的免疫应答细胞。微环境变化（如缺氧和营养不良）会导致未折叠和错误折叠的蛋白质在管腔内聚集，从而诱发内质网（ER）应激。 ER应激及其下游信号通路与免疫原性和肿瘤耐药性密切相关。 ER 应激在免疫细胞内的一系列过程和 BC 细胞的进展中发挥着关键作用，包括细胞增殖、自噬、细胞凋亡和对治疗的抵抗。最近的研究越来越认识到天然化合物通过 ER 应激诱导表现出抗 BC 特性的潜力。尽管如此，这些天然化合物的功效仍然低于免疫检查点抑制剂（ICIs）。目前，ER应激介导的免疫原性细胞死亡（ICD）途径更令人鼓舞，它可以通过介导免疫干性来增强ICI反应。本文概述了了解 ER 应激如何影响肿瘤免疫及其对 BC 的影响的最新进展。针对这一途径可能很快就会成为乳腺癌的一种引人注目的治疗策略。