By analyzing datasets from patient cohorts and performing systematic HLA peptidomic and immunoreactivity analyses of cells overexpressing the immunoproteasome subunits, we demonstrate that the overexpression of PSMB8 and PSMB9 results in enhanced reactivity of TILs toward melanoma cells, as a consequence of an altered repertoire of presented antigens. Here, PSMB9 is linked to melanoma.