Anti-PD-1/PD-L1 therapy augments lenvatinib's efficacy by favorably altering the immune microenvironment of murine anaplastic thyroid cancer.
Animals
Antineoplastic Agents
/ pharmacology
B7-H1 Antigen
/ antagonists & inhibitors
CD8-Positive T-Lymphocytes
/ cytology
Cell Line, Tumor
Cell Proliferation
Epithelial-Mesenchymal Transition
Female
Humans
Mice
Myeloid-Derived Suppressor Cells
/ cytology
Phenylurea Compounds
/ pharmacology
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Protein Kinase Inhibitors
/ pharmacology
Quinolines
/ pharmacology
T-Lymphocytes, Regulatory
/ cytology
Thyroid Carcinoma, Anaplastic
/ drug therapy
Thyroid Neoplasms
/ drug therapy
Tumor Microenvironment
/ immunology
anaplastic thyroid cancer
combination therapy
lenvatinib
orthotopic mouse model
programmed cell death-1
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 05 2019
01 05 2019
Historique:
received:
26
04
2018
revised:
08
10
2018
accepted:
22
10
2018
pubmed:
6
12
2018
medline:
9
8
2019
entrez:
6
12
2018
Statut:
ppublish
Résumé
Patients with anaplastic thyroid cancer (ATC) have an extremely poor prognosis despite multimodal therapy with surgery and chemoradiation. Lenvatinib, a multi-targeted tyrosine kinase inhibitor, as well as checkpoint inhibitors targeting the programmed cell death pathway, have proven effective in some patients with advanced thyroid cancer. Combination of these therapies is a potential means to boost effectiveness and minimize treatment resistance in ATC. We utilized our novel immunocompetent murine model of orthotopic ATC to demonstrate that lenvatinib led to significant tumor shrinkage and increased survival, while combination therapy led to dramatic improvements in both. Lenvatinib monotherapy increased tumor-infiltrating macrophages, CD8
Substances chimiques
Antineoplastic Agents
0
B7-H1 Antigen
0
Cd274 protein, mouse
0
Pdcd1 protein, mouse
0
Phenylurea Compounds
0
Programmed Cell Death 1 Receptor
0
Protein Kinase Inhibitors
0
Quinolines
0
lenvatinib
EE083865G2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
2266-2278Subventions
Organisme : National Institute of Allergy and Infectious Diseases
ID : P01AI056299P01AI123086
Pays : International
Organisme : NCI NIH HHS
ID : 1R01CA149738P50CA101942
Pays : United States
Organisme : NIDDK NIH HHS
ID : 5T32DK00702842
Pays : United States
Informations de copyright
© 2018 UICC.