Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 06 2022
27 06 2022
Historique:
received:
07
04
2021
accepted:
09
06
2022
entrez:
27
6
2022
pubmed:
28
6
2022
medline:
30
6
2022
Statut:
epublish
Résumé
Few patients with triple negative breast cancer (TNBC) benefit from immune checkpoint inhibitors with complete and durable remissions being quite rare. Oncogenes can regulate tumor immune infiltration, however whether oncogenes dictate diminished response to immunotherapy and whether these effects are reversible remains poorly understood. Here, we report that TNBCs with elevated MYC expression are resistant to immune checkpoint inhibitor therapy. Using mouse models and patient data, we show that MYC signaling is associated with low tumor cell PD-L1, low overall immune cell infiltration, and low tumor cell MHC-I expression. Restoring interferon signaling in the tumor increases MHC-I expression. By combining a TLR9 agonist and an agonistic antibody against OX40 with anti-PD-L1, mice experience tumor regression and are protected from new TNBC tumor outgrowth. Our findings demonstrate that MYC-dependent immune evasion is reversible and druggable, and when strategically targeted, may improve outcomes for patients treated with immune checkpoint inhibitors.
Identifiants
pubmed: 35760778
doi: 10.1038/s41467-022-31238-y
pii: 10.1038/s41467-022-31238-y
pmc: PMC9237085
doi:
Substances chimiques
B7-H1 Antigen
0
Immune Checkpoint Inhibitors
0
Proto-Oncogene Proteins c-myc
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3671Subventions
Organisme : NCI NIH HHS
ID : F32 CA243548
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM136547
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063720
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA223817
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA108462
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
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