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 (2018) reports that transforming growth factor beta (TGFβ) attenuates anti-tumour immunity by promoting T cell exclusion from the tumour microenvironment, thereby limiting response to PD-L1 checkpoint blockade. The authors demonstrate that TGFβ signalling suppresses T cell infiltration through multiple mechanisms, as suggested by their analysis of patient samples and preclinical models. These findings suggest that combining TGFβ pathway inhibition with PD-L1 blockade may enhance immunotherapy efficacy in resistant tumours.

UK applicability

The mechanistic insights may inform development of combination immunotherapy strategies applicable to UK cancer treatment protocols, particularly for patients with TGFβ-driven immune exclusion. However, direct clinical translation would require validation in UK patient populations and integration with NHS treatment pathways.

Key measures

T cell infiltration density, TGFβ signalling activation, tumour response to anti-PD-L1 therapy, immune cell populations in tumour microenvironment

Outcomes reported

The study examined mechanisms of resistance to PD-L1 checkpoint inhibitor therapy, specifically investigating how transforming growth factor beta (TGFβ) contributes to T cell exclusion from tumours. The research measured tumour response, T cell infiltration, and TGFβ pathway activation in patient samples and preclinical models.

Theme
Nutrition & health
Subject
Other / interdisciplinary
Study type
Research
Study design
Laboratory / mechanistic study with clinical validation
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/nature25501
Catalogue ID
BFmommpjky-1vk9qq

Topic tags

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