From oncogenesis to prognosis - the roles of the immunoproteasome in cancer

Sep 23, 2026

Uploaded by Terk

Review of the immunoproteasome’s (ImP) roles in cancer progression, prognosis, and treatment response. 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. The review links ImP to oncogenesis, anti-tumor immunity, and clinical outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

ImP structure

Baseline expression in cancer cells

Oncogenesis and progression

Anti-tumor immune response

Outcomes

TYPE Review PUBLISHED 08 July 2025 DOI 10.3389/fimmu.2025.1603816 OPEN ACCESS EDITED BY Chunhua Song, The Ohio State University, United States REVIEWED BY Byung-Gyu Kim, Case Western Reserve University, United States Jiacheng Jin, The Ohio State University, United States *CORRESPONDENCE Marie-Claude Bourgeois-Daigneault marie-claude. bourgeois-daigneault@ [umontreal.ca](umontreal.ca) RECEIVED 01 April 2025 ACCEPTED 23 June 2025 PUBLISHED 08 July 2025 CITATION Be´ land D, Viens M, Kalin EM and Bourgeois-Daigneault M-C (2025) From oncogenesis to prognosis: the roles of the immunoproteasome in cancer. Front. Immunol. 16:1603816 . doi: 10.3389/fimmu.2025.1603816 COPYRIGHT © 2025 Be´ land, Viens, Kalin and Bourgeois-Daigneault. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The 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. From oncogenesis to prognosis: the roles of the immunoproteasome in cancer Delphine 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* 1Cancer 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 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 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. KEYWORDS immunoproteasome, cancer, oncogenesis, anti-tumor immunity, clinical outcome 1 Introduction The 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 Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) Be´land et al. 10.3389/fimmu.2025.1603816 Baseline Exp

FAQs

What is the immunoproteasome and why is it important in cancer?

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.

How does the immunoproteasome connect to anti-tumor immunity?

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.

What does the review say about the relationship between immunoproteasome activity and prognosis?

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.

Sep 23, 2026

Uploaded by Terk