TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells

Journal: Nature

Published: 2018-02-22

DOI: 10.1038/nature25501

Affiliations: 9

Authors: 42

Go to article

Research Highlight

How to improve cancer immunotherapy

© Ariel Skelley/DigitalVision/Getty

© Ariel Skelley/DigitalVision/Getty

Blocking a critical growth factor in a tumour’s microenvironment could boost the cancer-killing potential of immunotherapy.

An international team led by scientists from Genentech, a Roche subsidiary, examined tumour samples from hundreds of patients with advanced-stage urinary cancers. All of the patients had received atezolizumab, a drug that blocks an ‘off switch’ signal that tumours use to ward off an immune onslaught, but only 22 per cent of them responded favourably.

The researchers found a strong association between the lack of drug response and the presence of cells in the tumour surroundings that expressed high levels of transforming growth factor β (TGFβ), a protein that keeps cancer-killing T-cells from reaching the tumour core.

In a mouse model of breast cancer, delivering a drug that targets TGFβ along with a mouse version of atezolizumab allowed more T-cells to penetrate the tumours, triggering tumour shrinkage. The findings, described in Nature, suggest that this dual therapeutic strategy merits further clinical testing in patients.

Supported content

  1. Nature 554, 544–548 (2018). doi: 10.1038/nature25501
Institutions Share
Genentech, Inc., United States of America (USA) 0.79
Lund University (LU), Sweden 0.05
Fios Genomics, United Kingdom (UK) 0.05
Netherlands Cancer Institute (NKI), Netherlands 0.02
Memorial Sloan Kettering Cancer Center (MSKCC), United States of America (USA) 0.02
UCSF Medical Center, United States of America (USA) 0.02
Queen Mary University of London (QMUL), United Kingdom (UK) 0.02
Institute Gustave-Roussy (IGR), France 0.01
University of Paris-Sud (UPSud), France 0.01