Proteotoxic stress response drives T cell exhaustion and immune evasion.

ABSTRACT: Chronic infections and cancer cause T cell dysfunction known as exhaustion. This cell state is caused by persistent antigen exposure, suboptimal co-stimulation and a plethora of hostile factors that dampen protective immunity and limit the efficacy of immunotherapies^1-4. The mechanisms that underlie T cell exhaustion remain poorly understood. Here we analyse the proteome of CD8⁺ exhausted T (T_ex) cells across multiple states of exhaustion in the context of both chronic viral infections and cancer. We show that there is a non-stochastic pathway-specific discordance between mRNA and protein dynamics between T effector (T_eff) and T_ex cells. We identify a distinct proteotoxic stress response (PSR) in T_ex cells, which we term T

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12657239 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature