Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

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

Sanjeev Mariathasan, Shannon J. Turley, Dorothee Nickles, Alessandra Castiglioni, Kobe Yuen, Yulei Wang, Edward E. Kadel, Hartmut Koeppen, Jillian L. Astarita, Rafael Cubas, Suchit Jhunjhunwala, Romain Banchereau, Yagai Yang, Yinghui Guan, Cécile Chalouni, James Ziai, Yasin Şenbabaoğlu, Stephen P. Santoro, Daniel Sheinson, Jeffrey Hung, Jennifer M. Giltnane, Andrew A. Pierce, Kathryn Mesh, Steve Lianoglou, Johannes Riegler, Richard A.D. Carano, Pontus Eriksson, Mattias Höglund, Loan Somarriba, Daniel L. Halligan, Michiel S. van der Heijden, Yohann Loriot, Jonathan E. Rosenberg, Lawrence Fong, Ira Mellman, Daniel S. Chen, Marjorie Green, Christina Louise Derleth, Gregg Fine, Priti S. Hegde, Richard Bourgon, Thomas Powles

Nature · 2018

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Summary

This Nature study, co-authored by Mariathasan and colleagues, examines the role of transforming growth factor beta (TGFβ) as a negative regulator of anti-PD-L1 checkpoint immunotherapy efficacy. The authors present evidence suggesting that TGFβ contributes to T cell exclusion from the tumour microenvironment, thereby attenuating therapeutic response. The work implies that targeting TGFβ signalling alongside PD-L1 blockade may enhance immunotherapy outcomes in certain tumour types.

UK applicability

As a fundamental mechanistic study of cancer immunotherapy, this work is relevant to UK oncology research and clinical practice through its potential to inform combination immunotherapy strategies. The findings may have implications for treatment protocols in UK cancer centres, particularly for tumours resistant to checkpoint inhibitor monotherapy.

Key measures

T cell infiltration, tumour response rates, TGFβ signalling pathway activity, immune cell composition in tumour microenvironment

Outcomes reported

The study investigated how transforming growth factor beta (TGFβ) influences tumour response to anti-PD-L1 immunotherapy and the mechanisms by which it excludes T cells from the tumour microenvironment.

Theme
Nutrition & health
Subject
Other / interdisciplinary
Study type
Research
Study design
Laboratory / in vitro and translational research
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/nature25501
Catalogue ID
BFmokjoc86-g9u7g5

Topic tags

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