Here, we reveal how O-sialoglycoprotein endopeptidase (OSGEP), catalysing the tRNA modification N<sup>6</sup>-threonylcarbamoyladenosine (t<sup>6</sup>A), drives protein homeostasis in cancer cells to maintain T-cell exclusion and prevent anti-tumour immune response. Here, OSGEP is linked to neoplasm.