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The article explains how proteasomes maintain protein homeostasis and how proteasome-generated fragments feed the MHC-I antigen presentation pathway for immune recognition. It details ImP-specific cleavage, its constitutive and inducible expression in immune and other cells, and its presence in the tumor microenvironment. 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It supports antigen presentation and is expressed or induced in immune contexts and within tumors, influencing cancer progression and outcomes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the immunoproteasome connect to anti-tumor immunity?",{"text":117,"@type":113},"Immunoproteasome processing contributes to MHC-I presentation on cell surfaces, enabling immune recognition. The review emphasizes its role across immune response stages within the tumor microenvironment.",{"name":119,"@type":110,"acceptedAnswer":120},"What does the review say about the relationship between immunoproteasome activity and prognosis?",{"text":121,"@type":113},"The review summarizes how immunoproteasome expression patterns in tumors can correlate with favorable or unfavorable outcomes across different cancer types. 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Immunol. 16:1603816 .  \ndoi: 10.3389/fimmu.2025.1603816  \nCOPYRIGHT  \n© 2025 Be´ land, Viens, Kalin and  \nBourgeois-Daigneault. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) .  \nThe use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nFrom oncogenesis to prognosis: the roles of the immunoproteasome in cancer  \nDelphine B´eland 1,2,3, M´elissa Viens 1,2,3, Emma Mary Kalin 1,2,3 and Marie-Claude Bourgeois-Daigneault 1,2,3*  \n1Cancer Axis and Institut du cancer de Montre´ al, Centre Hospitalier de l ’ Universite´ de Montre´ al (CHUM) Research Centre, Montreal, QC, Canada, 2 Immunopathology Axis, Centre Hospitalier del ’ Universite´ de Montre´al (CHUM) Research Centre, Montreal, QC, Canada, 3 Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, Montreal, QC, Canada  \nThe 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 proinflammatory 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.  \nKEYWORDS  \nimmunoproteasome, cancer, oncogenesis, anti-tumor immunity, clinical outcome  \n1 Introduction  \nThe constitutive 26S proteasome (CP) is a large intracellular proteolytic complex that is primarily known for its key role in protein homeostasis (1) . Protein degradation by the CP allows for the recycling of misfolded and damaged proteins and also modulates various cellular functions by degrading key pathway regulators, as well as other components (2–4) . Importantly, the CP also contributes to antigen presentation by major histocompatibility class I (MHC-I) molecules. Indeed, it cleaves proteins into peptides that are then fed into the pathway for loading onto MHC-I molecules, cell surface display and presentation to immune cells (5) . Other types of proteasomes are also found in mammals. As such, the thymoproteasome, the spermatoproteasome and the ImP are expressed in different  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \nBe´land et al. 10.3389/fimmu.2025.1603816  \nBaseline Exp","cbCaik33zAnNqWu4","https://ap.wps.com/l/cbCaik33zAnNqWu4","pdf",2941155,12,"English","# Introduction\n# ImP structure\n# Baseline expression in cancer cells\n# Oncogenesis and progression\n# Anti-tumor immune response\n# Outcomes","[{\"question\":\"What is the immunoproteasome and why is it important in cancer?\",\"answer\":\"The immunoproteasome is a proteasome variant that preferentially generates MHC-I-compatible peptide fragments. It supports antigen presentation and is expressed or induced in immune contexts and within tumors, influencing cancer progression and outcomes.\"},{\"question\":\"How does the immunoproteasome connect to anti-tumor immunity?\",\"answer\":\"Immunoproteasome processing contributes to MHC-I presentation on cell surfaces, enabling immune recognition. The review emphasizes its role across immune response stages within the tumor microenvironment.\"},{\"question\":\"What does the review say about the relationship between immunoproteasome activity and prognosis?\",\"answer\":\"The review summarizes how immunoproteasome expression patterns in tumors can correlate with favorable or unfavorable outcomes across different cancer types. It also discusses links to therapy response, including immune checkpoint inhibitor outcomes.\"}]","From oncogenesis to prognosis - the roles of the immunoproteasome in cancer | PDF",1790194791]