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

Journal: Nature Medicine

Published: 2018-06-11

DOI: 10.1038/s41591-018-0057-z

Affiliations: 13

Authors: 19

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Research Highlight

‘Exhausted’ cells may be invigorated against cancer

© JUAN GAERTNER/SCIENCE PHOTO LIBRARY/Getty

© JUAN GAERTNER/SCIENCE PHOTO LIBRARY/Getty

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.

Supported content

  1. Nature Medicine 24, 994–1004 (2018). doi: 10.1038/s41591-018-0057-z
Institutions FC
Department of Biomedicine Basel, Switzerland 0.26
Roche Pharma Research and Early Development (Roche pRED), Switzerland 0.21
Cantonal Hospital Baselland (KSBL), Switzerland 0.18
University Hospital Basel (USB), UB, Switzerland 0.16
Division of Molecular Oncology and Immunology, NKI, Netherlands 0.08
Ludwig Center for Cancer Research, UNIL, Switzerland 0.05
Department of Oncology, UB, Switzerland 0.03
Oxford University Hospitals NHS Trust (OUH), United Kingdom (UK) 0.02
University of Oxford, United Kingdom (UK) 0.02

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