Journal: Frontiers in Oncology

Article Title: Rewiring tumor visibility: The immunopeptidome as a dynamic interface between antigen processing, microenvironmental stress, and immune recognition

doi: 10.3389/fonc.2025.1691719

Figure Lengend Snippet: Context-dependent dual roles of the immunoproteasome in cancer. The immunoproteasome (IP) exerts divergent functions depending on tumor type and microenvironmental context. On the pro-tumor side (red), IP activity sustains chronic inflammation, promotes IL-17/LMP7-driven prostate cancer progression, maintains AML stemness (PSMB10, UBE2N), rewires epigenetic and metabolic programs (DNMT1/3B loss, MCL-1 survival), and supports immune evasion via the USP24–STAT3–PD1 axis. Conversely, in immunogenic contexts (green), IP enhances tumor suppression by broadening the immunopeptidome and unmasking neoantigens, promoting CD8 + T-cell responses, with PSMB9 acting as a tumor suppressor in melanoma, glutamate flux inhibition boosting antigenicity in CRC, and dual MCL-1/MEK inhibition restoring therapy sensitivity in TNBC/IBC. High IP expression aligns with favorable prognosis in melanoma, bladder cancer, and TNBC. Notably, IP is dispensable for leukemia infected-cell vaccine efficacy (exception). Collectively, these findings position the IP as a context-dependent regulator, balancing between tumor-promoting inflammation and antigen-driven immune surveillance.

Article Snippet: AML – UBE2N and proteostasis , UBE2N stabilizes proteins via K63 ubiquitination; its inhibition triggers K48-linked degradation through immunoproteasome, suppressing AML. , UBE2N is a vulnerability in immunoproteasome-positive AML; inhibition may serve as therapeutic strategy. , ( ) .

Techniques: Activity Assay, Immunopeptidomics, Inhibition, Expressing, Infection