{"entity":{"id":"t-cell-exhaustion-term","kind":"term","name":"T-cell exhaustion and CAR-T persistence","aka":["exhaustion","exhausted T cells","T-cell fitness","T cell fitness","T-cell dysfunction","CAR-T persistence","CAR persistence","CAR-T expansion","peak expansion","in vivo expansion","B-cell aplasia","loss of persistence","memory phenotype","stem-like T cells"],"tldr":"Immune T cells that have been fighting too long become 'exhausted': sluggish, covered in inhibitory receptors, unable to kill. It limits both the patient's natural anti-tumour response and how long engineered CAR-T cells keep working (persistence).","summary":"Exhaustion is driven by chronic antigen exposure and marked by PD-1, TIM-3, LAG-3 and TOX expression; checkpoint inhibitors partly reverse it, which is their mechanism. For CAR-T, the fitness of the patient's starting T cells (damaged by prior chemotherapy, especially bendamustine) predicts expansion and response, and peak expansion and persistence correlate with durable remission; ongoing B-cell aplasia is a convenient marker that CD19 CAR-T cells are still active. Engineering answers include 4-1BB costimulation (longer persistence than CD28), armoured CARs, knockout of exhaustion-associated genes, and collecting cells earlier in the disease course. Persistence matters less when the tumour is eliminated quickly, as in ALL.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/T_cell_exhaustion","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/T_cell_exhaustion"}],"tags":[],"related":["antigen-escape","cold-vs-hot","hypogammaglobulinaemia"],"cancers":[],"sections":["cell-therapy","immunotherapy"],"technologies":["car-t","armored-car","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},"route":"/terms/t-cell-exhaustion-term/","neighbours":{"term":[{"id":"antigen-escape","kind":"term","name":"Antigen escape (antigen loss, lineage switch)","route":"/terms/antigen-escape/"},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"hypogammaglobulinaemia","kind":"term","name":"Hypogammaglobulinaemia and infection risk after B-cell therapies","route":"/terms/hypogammaglobulinaemia/"}],"section":[{"id":"cell-therapy","kind":"section","name":"Cell Therapy","route":"/fronts/cell-therapy/"},{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"armored-car","kind":"technology","name":"Armoured, logic-gated & next-gen CARs","route":"/technologies/armored-car/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]}}