During malignant transformation and cancer progression, tumor cells face both intrinsic and extrinsic stress, endoplasmic reticulum (ER) stress in particular. To survive and proliferate, tumor cells use multiple stress response pathways to mitigate ER stress, promoting disease aggression and treatment resistance. Among the stress response pathways is ER-associated degradation (ERAD), which consists of multiple components and steps working together to ensure protein quality and quantity. In addition to its established role in stress responses and tumor cell survival, ERAD has recently been shown to regulate tumor immunity. Here we summarize current knowledge on how ERAD promotes protein degradation, regulates immune cell development and function, participates in antigen presentation, exerts paradoxical roles on tumorigenesis and immunity, and thus impacts current cancer therapy. Collectively, ERAD is a critical protein homeostasis pathway intertwined with cancer development and tumor immunity. Of particular importance is the need to further unveil ERAD’s enigmatic roles in tumor immunity to develop effective targeted and combination therapy for successful treatment of cancer.

在恶性转化和癌症进展过程中，肿瘤细胞面临内在和外在压力，尤其是内质网 (ER) 压力。为了生存和增殖，肿瘤细胞使用多种应激反应途径来减轻内质网应激，促进疾病侵袭和治疗抵抗。应激反应途径包括内质网相关降解 (ERAD)，它由多个组件和步骤组成，共同确保蛋白质的质量和数量。除了在应激反应和肿瘤细胞存活中的既定作用外，ERAD 最近还被证明可以调节肿瘤免疫。在这里，我们总结了当前关于 ERAD 如何促进蛋白质降解、调节免疫细胞发育和功能、参与抗原呈递、在肿瘤发生和免疫中发挥矛盾作用的知识，从而影响当前的癌症治疗。总的来说，ERAD 是与癌症发展和肿瘤免疫交织在一起的关键蛋白质稳态途径。特别重要的是需要进一步揭示 ERAD 在肿瘤免疫中的神秘作用，以开发有效的靶向和联合疗法以成功治疗癌症。