A transcriptionally and functionally distinct PD-1 CD8 T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade

‘Exhausted’ cells may be invigorated against cancer

26 December 2018

The best way to differentiate between cancer-fighting T cells in lung tumours may be to look at the number of immune-dampening ‘checkpoint’ molecules on the cell surface.

A team that included scientists from Roche’s Pharmaceutical Research and Early Development studied biopsy material from patients with advanced non-small cell lung cancer. To their surprise, they found that T cells crowded with PD-1 checkpoint proteins on their surfaces — usually a sign of immune ‘exhaustion’ — had the greatest capacity to recognize tumour tissue.

The PD-1–enriched T cells showed many signs of dysfunction, yet they expressed a key signalling molecule that recruited other immune cells to the tumour surroundings. This could explain why the presence of PD-1–elevated T cells was strongly predictive of how patients respond to cancer immunotherapy.

This unique T cell population thus offers a promising new biomarker for identifying patients most likely to benefit from the drug-treatment strategy.

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References

1. Nature Medicine 24, 994–1004 (2018). doi: 10.1038/s41591-018-0057-z