Immune checkpoint proteins are expressed on tumour or immune cells and their inhibition using immune checkpoint inhibitors (ICIs) can enhance anti-tumour immunity. However, currently used biomarkers do not always reliably predict response, highlighting the need to find additional biomarkers.

Work by Kalaora et al. demonstrates that expression of the immunoproteasome, a specialized form of the proteasome, could be a potential biomarker for ICI response in melanoma. The proteasome degrades proteins into smaller peptides that can then be displayed on the cell surface (known as antigen presentation) to alert immune cells. The immunoproteasome is predominantly expressed in antigen-presenting immune cells and can be induced in epithelial cells upon exposure to inflammatory cytokines to trigger an immune response. Using transcriptomics data from patients with melanoma and healthy controls, the authors showed that expression of the immunoproteasome catalytic subunits (PSMB8 and PSMB9) is higher in tumours than in normal tissues. Patients with this high immunoproteasome expression exhibited a better overall survival than those with low expression, and displayed enrichment of cytotoxic immune cells in the tumour, indicating an increased immune response.