Béland Delphine, Viens Mélissa, Kalin Emma Mary, Bourgeois-Daigneault Marie-Claude
Cancer Axis and Institut du cancer de Montréal, Centre Hospitalier de l'Université de Montréal (CHUM) Research Centre, Montreal, QC, Canada.
Immunopathology Axis, Centre Hospitalier de l'Université de Montréal (CHUM) Research Centre, Montreal, QC, Canada.
Front Immunol. 2025 Jul 8;16:1603816. doi: 10.3389/fimmu.2025.1603816. eCollection 2025.
The proteasome (prosome, macropain) is a key cellular organelle responsible primarily for protein homeostasis, by degrading damaged or misfolded proteins. Proteasome-processed protein fragments can then be further trimmed and funneled to the major histocompatibility complex class I (MHC-I) antigen presentation pathway for cell surface display and immune recognition. Various types of proteasomes can be found in mammalian cells with different expression patterns and cleavage abilities. As such, the immunoproteasome (ImP) preferentially cleaves proteins to yield MHC-I-compatible fragments. It is constitutively expressed by some immune cells and can be induced by pro-inflammatory signals. Interestingly, it was also found to be expressed in multiple types of cancers and proteasome activity can be modulated by some cancer therapies. A better understanding of its impact on cancer progression, prognosis and treatment response is therefore needed to guide treatment decisions. In this review, we focus on the multiple roles of the ImP in cancer, including its interplay with the immune system, as well as its impact on patient outcomes.
蛋白酶体（蛋白酶体、大蛋白酶）是一种关键的细胞器，主要通过降解受损或错误折叠的蛋白质来维持蛋白质稳态。蛋白酶体处理后的蛋白质片段随后可被进一步修剪，并进入主要组织相容性复合体I类（MHC-I）抗原呈递途径，用于细胞表面展示和免疫识别。在哺乳动物细胞中可以发现各种类型的蛋白酶体，它们具有不同的表达模式和切割能力。因此，免疫蛋白酶体（ImP）优先切割蛋白质以产生与MHC-I兼容的片段。它在一些免疫细胞中组成性表达，并可由促炎信号诱导。有趣的是，人们还发现它在多种癌症中表达，并且蛋白酶体活性可被一些癌症治疗所调节。因此，需要更好地了解其对癌症进展、预后和治疗反应的影响，以指导治疗决策。在这篇综述中，我们重点关注ImP在癌症中的多种作用，包括其与免疫系统 的相互作用，以及对患者预后的影响。
