<<< Full experiment listing

PXD015804

PXD015804 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeting immunosuppressive macrophages overcomes PARP-inhibitor resistance in BRCA1-associated triple-negative breast cancer
DescriptionDespite objective responses to PARP inhibition and improvements in progression-free survival compared to standard chemotherapy in patients with BRCA-associated triple-negative breast cancer (TNBC), benefits are transitory. Using high dimensional single-cell profiling of human TNBC, here we demonstrate that macrophages are the predominant infiltrating immune cell type in BRCA-associated TNBC. Through multi-omics profiling we show that PARP inhibitors enhance both anti- and pro-tumor features of macrophages through glucose and lipid metabolic reprogramming driven by the sterol regulatory element-binding protein 1 (SREBP-1) pathway. Combined PARP inhibitor therapy with CSF-1R blocking antibodies significantly enhanced innate and adaptive anti-tumor immunity and extends survival in BRCA-deficient tumors in vivo and is mediated by CD8+ T-cells. Collectively, our results uncover macrophage-mediated immune suppression as a liability of PARP inhibitor treatment and demonstrate combined PARP inhibition and macrophage targeting therapy induces a durable reprogramming of the tumor microenvironment, thus constituting a promising therapeutic strategy for TNBC.
HostingRepositoryPRIDE
AnnounceDate2021-03-25
AnnouncementXMLSubmission_2021-03-24_23:42:39.215.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJennifer Guerriero
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-10-14 02:04:33ID requested
12021-03-24 23:42:40announced
Publication List
Mehta AK, Cheney EM, Hartl CA, Pantelidou C, Oliwa M, Castrillon JA, Lin JR, Hurst KE, de Oliveira Taveira M, Johnson NT, Oldham WM, Kalocsay M, Berberich MJ, Boswell SA, Kothari A, Johnson S, Dillon DA, Lipschitz M, Rodig S, Santagata S, Garber JE, Tung N, Yélamos J, Thaxton JE, Mittendorf EA, Sorger PK, Shapiro GI, Guerriero JL, Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer. Nat Cancer, 2(1):66-82(2021) [pubmed]
Keyword List
submitter keyword: TAM (tumor associated macrophage), PARP, TMT, Lumos
Contact List
Jennifer L. Guerriero, PhD
contact affiliationDirector of The Breast Tumor Immunology Laboratory Women’s Cancer Program Dana-Farber Cancer Institute Instructor in Medicine Harvard Medical School
contact emailjennifer_guerriero@dfci.harvard.edu
lab head
Jennifer Guerriero
contact affiliationDana-Farber Cancer Institute
contact emailJennifer_Guerriero@dfci.harvard.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
PRIDE project URI
Repository Record List
[ + ]