Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer.
Animals
Antineoplastic Agents, Immunological
/ pharmacology
B7-H1 Antigen
/ antagonists & inhibitors
CD8-Positive T-Lymphocytes
/ drug effects
Cell Line, Tumor
/ transplantation
Cell Proliferation
/ drug effects
Disease Models, Animal
Drug Resistance, Neoplasm
/ drug effects
HEK293 Cells
Humans
Membrane Proteins
/ antagonists & inhibitors
Mice
Neoplasms
/ drug therapy
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
T-Lymphocytes, Regulatory
/ drug effects
Transforming Growth Factor beta1
/ antagonists & inhibitors
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 09 2020
11 09 2020
Historique:
received:
21
01
2020
accepted:
20
07
2020
entrez:
12
9
2020
pubmed:
13
9
2020
medline:
2
10
2020
Statut:
epublish
Résumé
TGF-β1, β2 and β3 bind a common receptor to exert vastly diverse effects in cancer, supporting either tumor progression by favoring metastases and inhibiting anti-tumor immunity, or tumor suppression by inhibiting malignant cell proliferation. Global TGF-β inhibition thus bears the risk of undesired tumor-promoting effects. We show that selective blockade of TGF-β1 production by Tregs with antibodies against GARP:TGF-β1 complexes induces regressions of mouse tumors otherwise resistant to anti-PD-1 immunotherapy. Effects of combined GARP:TGF-β1/PD-1 blockade are immune-mediated, do not require FcγR-dependent functions and increase effector functions of anti-tumor CD8
Identifiants
pubmed: 32917858
doi: 10.1038/s41467-020-17811-3
pii: 10.1038/s41467-020-17811-3
pmc: PMC7486376
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
B7-H1 Antigen
0
Cd274 protein, mouse
0
Lrrc32 protein, mouse
0
Membrane Proteins
0
Pdcd1 protein, mouse
0
Programmed Cell Death 1 Receptor
0
Tgfb1 protein, mouse
0
Transforming Growth Factor beta1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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