Durvalumab Combined with Immunomodulatory Drugs (IMiD) Overcomes Suppression of Antitumor Responses due to IMiD-induced PD-L1 Upregulation on Myeloma Cells.
Animals
Antibodies, Monoclonal
/ pharmacology
Antineoplastic Agents, Immunological
/ pharmacology
Apoptosis
/ drug effects
B-Cell Maturation Antigen
/ metabolism
B7-H1 Antigen
/ genetics
Biomarkers, Tumor
Cell Line, Tumor
Cell Survival
/ drug effects
Disease Models, Animal
Gene Expression Regulation, Neoplastic
/ drug effects
Gene Knockdown Techniques
Humans
Ikaros Transcription Factor
/ metabolism
Immunomodulating Agents
/ pharmacology
Immunophenotyping
Mice
Multiple Myeloma
/ drug therapy
Programmed Cell Death 1 Receptor
Proteolysis
Signal Transduction
/ drug effects
T-Lymphocytes
/ drug effects
Tumor Necrosis Factor Ligand Superfamily Member 13
/ metabolism
Xenograft Model Antitumor Assays
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
31
03
2020
revised:
04
01
2021
accepted:
16
04
2021
pubmed:
22
4
2021
medline:
11
1
2022
entrez:
21
4
2021
Statut:
ppublish
Résumé
We previously showed that the interaction of programmed death-ligand 1 (PD-L1) on multiple myeloma (MM) cells with PD-1 not only inhibits tumor-specific cytotoxic T-lymphocyte activity via the PD-1 signaling pathway but also induces drug resistance via PD-L1-mediated reverse signals. We here examined the regulation of PD-L1 expression by immunomodulatory drugs (IMiDs) and antimyeloma effects of the anti-PD-L1 antibody durvalumab in combination with IMiDs. IMiDs induced PD-L1 expression on IMiD-insensitive MM cells and plasma cells from patients newly diagnosed with MM. Gene-expression profiling analysis demonstrated that not only PD-L1, but also a proliferation-inducing ligand (APRIL), was enhanced by IMiDs. PD-L1 induction by IMiDs was suppressed by using the APRIL inhibitor recombinant B-cell maturation antigen (BCMA)-Ig, the antibody against BCMA, or an MEK/ERK inhibitor in
Identifiants
pubmed: 33879556
pii: 1535-7163.MCT-20-0246
doi: 10.1158/1535-7163.MCT-20-0246
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antineoplastic Agents, Immunological
0
B-Cell Maturation Antigen
0
B7-H1 Antigen
0
Biomarkers, Tumor
0
CD274 protein, human
0
Immunomodulating Agents
0
Programmed Cell Death 1 Receptor
0
TNFRSF17 protein, human
0
Tnfsf13 protein, mouse
0
Tumor Necrosis Factor Ligand Superfamily Member 13
0
Ikaros Transcription Factor
148971-36-2
durvalumab
28X28X9OKV
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1283-1294Informations de copyright
©2021 American Association for Cancer Research.
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