# T-cell exhaustion and CAR-T persistence

Source: https://onco.cc/terms/t-cell-exhaustion-term/  
OnCo record `t-cell-exhaustion-term` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: 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

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/T_cell_exhaustion
- Wikipedia: https://en.wikipedia.org/wiki/T_cell_exhaustion

## Connected records

- terms: [Antigen escape (antigen loss, lineage switch)](https://onco.cc/terms/antigen-escape/), [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Hypogammaglobulinaemia and infection risk after B-cell therapies](https://onco.cc/terms/hypogammaglobulinaemia/)
- fronts: [Cell Therapy](https://onco.cc/fronts/cell-therapy/), [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- technologies: [Armoured, logic-gated & next-gen CARs](https://onco.cc/technologies/armored-car/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)

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