Proteomic atlas of T cell exhaustion defines proteostatic collapse

A multi-omic atlas of human T cell exhaustion reveals that dysfunctional T cells undergo broad remodeling of protein turnover and ubiquitin regulation that is not captured by transcriptomic analysis. The E3 ubiquitin ligase RNF166 regulates T cell persistence and anti-tumor function, highlighting proteostasis as a targetable axis for improving immunotherapy.