NR4A transcription factors limit CAR T cell function in solid tumours.

ABSTRACT: T cells expressing chimeric antigen receptors (CAR T cells) targeting human CD19 (hCD19) have shown clinical efficacy against B cell malignancies^1,2. CAR T cells have been less effective against solid tumours^3-5, in part because they enter a hyporesponsive ('exhausted' or 'dysfunctional') state^6-9 triggered by chronic antigen stimulation and characterized by upregulation of inhibitory receptors and loss of effector function. To investigate the function of CAR T cells in solid tumours, we transferred hCD19-reactive CAR T cells into hCD19⁺ tumour-bearing mice. CD8⁺CAR⁺ tumour-infiltrating lymphocytes and CD8⁺ endogenous tumour-infiltrating lymphocytes expressing the inhibitory receptors PD-1 and TIM3 exhibited simil

SUBMITTER: Chen J 

PROVIDER: S-EPMC6546093 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature