What question did this study set out to answer?

Determine whether selectively inhibiting TGF-β1 produced by GARP-expressing regulatory T cells can overcome resistance to PD-1/PD-L1 blockade without triggering the toxicities of global TGF-β inhibition.

September 11, 2020Nature CommunicationsOpen Access

Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer

View Full Paper

Ask AI

Bookmark

Authors

GSGrégoire de Streel CBCharlotte Bertrand NCNicolas Chalon

Discussion

Member takes

Overview

Preclinical study demonstrates that selective GARP:TGF-β1 blockade overcomes anti-PD-1 resistance in resistant tumors, indicating a targeted approach to enhance cancer immunotherapy.

Key Points

Determine whether selectively inhibiting TGF-β1 produced by GARP-expressing regulatory T cells can overcome resistance to PD-1/PD-L1 blockade without triggering the toxicities of global TGF-β inhibition.
Evaluated antibodies targeting GARP:TGF-β1 complexes in combination with anti-PD-1 therapy in mouse tumor models resistant to PD-1 monotherapy.
Assessed anti-tumor CD8+ T-cell responses, intratumoral regulatory T-cell abundance, and FcγR dependence.
Examined the expression of GARP and TGF-β1 production by regulatory T cells in human melanoma metastases.
Combined GARP:TGF-β1 and anti-PD-1 blockade induced regressions in mouse tumors previously resistant to anti-PD-1 alone.
Therapeutic responses were immune-mediated and boosted CD8+ T-cell effector functions without depleting regulatory T cells, altering immune infiltration, or requiring FcγR activity.
GARP-expressing regulatory T cells actively producing TGF-β1 were detected in one-third of analyzed human melanoma metastases.

Cite This Study

Streel et al. (2020) studied this question.

synapsesocial.com/papers/6a734027a7d283abeec2370e https://doi.org/10.1038/s41467-020-17811-3

View Full Paper

Ask AI

Bookmark

September 11, 2020Nature CommunicationsOpen Access

Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer

View Full Paper

Ask AI

Bookmark

Authors

GSGrégoire de Streel CBCharlotte Bertrand NCNicolas Chalon

Discussion

Member takes

Overview

Preclinical study demonstrates that selective GARP:TGF-β1 blockade overcomes anti-PD-1 resistance in resistant tumors, indicating a targeted approach to enhance cancer immunotherapy.

Key Points

Determine whether selectively inhibiting TGF-β1 produced by GARP-expressing regulatory T cells can overcome resistance to PD-1/PD-L1 blockade without triggering the toxicities of global TGF-β inhibition.
Evaluated antibodies targeting GARP:TGF-β1 complexes in combination with anti-PD-1 therapy in mouse tumor models resistant to PD-1 monotherapy.
Assessed anti-tumor CD8+ T-cell responses, intratumoral regulatory T-cell abundance, and FcγR dependence.
Examined the expression of GARP and TGF-β1 production by regulatory T cells in human melanoma metastases.
Combined GARP:TGF-β1 and anti-PD-1 blockade induced regressions in mouse tumors previously resistant to anti-PD-1 alone.
Therapeutic responses were immune-mediated and boosted CD8+ T-cell effector functions without depleting regulatory T cells, altering immune infiltration, or requiring FcγR activity.
GARP-expressing regulatory T cells actively producing TGF-β1 were detected in one-third of analyzed human melanoma metastases.

Cite This Study

Streel et al. (2020) studied this question.

synapsesocial.com/papers/6a734027a7d283abeec2370e https://doi.org/10.1038/s41467-020-17811-3

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

View Full Paper

Ask AI

Bookmark