Interleukin-10 suppression enhances T-cell antitumor immunity and responses to checkpoint blockade in chronic lymphocytic leukemia.
Animals
Antibiotics, Antineoplastic
/ pharmacology
Apoptosis
B7-H1 Antigen
/ antagonists & inhibitors
CD8-Positive T-Lymphocytes
/ drug effects
Case-Control Studies
Cell Proliferation
Disease Models, Animal
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Immune Checkpoint Inhibitors
/ pharmacology
Interleukin-10
/ antagonists & inhibitors
Leukemia, Lymphocytic, Chronic, B-Cell
/ drug therapy
Lymphocyte Activation
/ immunology
Mice
Mice, Inbred NOD
Mice, SCID
Plicamycin
/ pharmacology
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
11
06
2020
accepted:
04
03
2021
revised:
15
02
2021
pubmed:
19
3
2021
medline:
31
12
2021
entrez:
18
3
2021
Statut:
ppublish
Résumé
T-cell dysfunction is a hallmark of B-cell Chronic Lymphocytic Leukemia (CLL), where CLL cells downregulate T-cell responses through regulatory molecules including programmed death ligand-1 (PD-L1) and Interleukin-10 (IL-10). Immune checkpoint blockade (ICB) aims to restore T-cell function by preventing the ligation of inhibitory receptors like PD-1. However, most CLL patients do not respond well to this therapy. Thus, we investigated whether IL-10 suppression could enhance antitumor T-cell activity and responses to ICB. Since CLL IL-10 expression depends on Sp1, we utilized a novel, better tolerated analogue of the Sp1 inhibitor mithramycin (MTM
Identifiants
pubmed: 33731852
doi: 10.1038/s41375-021-01217-1
pii: 10.1038/s41375-021-01217-1
pmc: PMC8446094
mid: NIHMS1680459
doi:
Substances chimiques
Antibiotics, Antineoplastic
0
B7-H1 Antigen
0
CD274 protein, human
0
Immune Checkpoint Inhibitors
0
Interleukin-10
130068-27-8
Plicamycin
NIJ123W41V
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3188-3200Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR000117
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA217255
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM130456
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA165990
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA217934
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA177558
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA165469
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001998
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM115261
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA239480
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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