Pharmacologic Suppression of B7-H4 Glycosylation Restores Antitumor Immunity in Immune-Cold Breast Cancers.
Animals
B7-H1 Antigen
/ antagonists & inhibitors
Benzamides
/ pharmacology
Cell Line, Tumor
Doxorubicin
/ pharmacology
Female
Glycosylation
HEK293 Cells
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Sulfonamides
/ pharmacology
Triple Negative Breast Neoplasms
/ drug therapy
Ubiquitination
V-Set Domain-Containing T-Cell Activation Inhibitor 1
/ antagonists & inhibitors
Journal
Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
02
04
2020
revised:
15
07
2020
accepted:
11
09
2020
pubmed:
18
9
2020
medline:
25
11
2021
entrez:
17
9
2020
Statut:
ppublish
Résumé
Despite widespread utilization of immunotherapy, treating immune-cold tumors has proved to be a challenge. Here, we report that expression of the immune checkpoint molecule B7-H4 is prevalent among immune-cold triple-negative breast cancers (TNBC), where its expression inversely correlates with that of PD-L1. Glycosylation of B7-H4 interferes with its interaction/ubiquitination by AMFR, resulting in B7-H4 stabilization. B7-H4 expression inhibits doxorubicin-induced cell death through the suppression of eIF2α phosphorylation required for calreticulin exposure vis-à-vis the cancer cells. NGI-1, which inhibits B7-H4 glycosylation causing its ubiquitination and subsequent degradation, improves the immunogenic properties of cancer cells treated with doxorubicin, enhancing their phagocytosis by dendritic cells and their capacity to elicit CD8
Identifiants
pubmed: 32938586
pii: 2159-8290.CD-20-0402
doi: 10.1158/2159-8290.CD-20-0402
pmc: PMC7710601
mid: NIHMS1630380
doi:
Substances chimiques
B7-H1 Antigen
0
Benzamides
0
CD274 protein, human
0
CID2519269
0
Sulfonamides
0
V-Set Domain-Containing T-Cell Activation Inhibitor 1
0
VTCN1 protein, human
0
Doxorubicin
80168379AG
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
1872-1893Subventions
Organisme : NCI NIH HHS
ID : R01 CA202963
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM108569
Pays : United States
Organisme : NIDDK NIH HHS
ID : P01 DK096990
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA060553
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103712
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA250110
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA202948
Pays : United States
Organisme : NLM NIH HHS
ID : R01 LM012011
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2020 American Association for Cancer Research.
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