Novel TGFβ Inhibitors Ameliorate Oral Squamous Cell Carcinoma Progression and Improve the Antitumor Immune Response of Anti-PD-L1 Immunotherapy.
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
05
11
2020
revised:
11
02
2021
accepted:
26
03
2021
pubmed:
15
4
2021
medline:
27
1
2022
entrez:
14
4
2021
Statut:
ppublish
Résumé
TGFβ is a key regulator of oral squamous cell carcinoma (OSCC) progression, and its potential role as a therapeutic target has been investigated with a limited success. This study evaluates two novel TGFβ inhibitors as mono or combinatorial therapy with anti-PD-L1 antibodies (α-PD-L1 Ab) in a murine OSCC model. Immunocompetent C57BL/6 mice bearing malignant oral lesions induced by 4-nitroquinoline 1-oxide (4-NQO) were treated for 4 weeks with TGFβ inhibitors mRER (i.p., 50 μg/d) or mmTGFβ2-7m (10 μg/d delivered by osmotic pumps) alone or in combination with α-PD-L1 Abs (7× i.p. of 100 μg/72 h). Tumor progression and body weight were monitored. Levels of bioactive TGFβ in serum were quantified using a TGFβ bioassay. Tissues were analyzed by immunohistology and flow cytometry. Therapy with mRER or mmTGFβ2-7m reduced tumor burden (
Identifiants
pubmed: 33850003
pii: 1535-7163.MCT-20-0944
doi: 10.1158/1535-7163.MCT-20-0944
pmc: PMC8172434
mid: NIHMS1692612
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Transforming Growth Factor beta
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1102-1111Subventions
Organisme : NCI NIH HHS
ID : R01 CA172886
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM058670
Pays : United States
Organisme : NIDCR NIH HHS
ID : U01 DE029759
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
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