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Staquicini, F.I.* ; Hajitou, A.* ; Driessen, W.H.* ; Proneth, B. ; Cardó-Vila, M.* ; Staquicini, D.I.* ; Markosian, C.* ; Hoh, M.* ; Cortez, M.* ; Hooda-Nehra, A.* ; Jaloudi, M.* ; Silva, I.T.* ; Buttura, J.* ; Nunes, D.* ; Dias-Neto, E.* ; Eckhardt, B.* ; Ruiz-Ramírez, J.* ; Dogra, P.* ; Wang, Z.* ; Cristini, V.* ; Trepel, M.* ; Anderson, R.* ; Sidman, R.L.* ; Gelovani, J.G.* ; Cristofanilli, M.* ; Hortobagy, G.* ; Bhujwalla, Z.M.* ; Burley, S.* ; Arap, W.* ; Pasqualini, R.*

Targeting a cell surface vitamin D receptor on tumor-associated macrophages in triple-negative breast cancer.

eLife 10:e65145 (2021)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Triple-negative breast cancer (TNBC) is an aggressive tumor with limited treatment options and poor prognosis. We applied the in vivo phage display technology to isolate peptides homing to the immunosuppressive cellular microenvironment of TNBC as a strategy for non-malignant target discovery. We identified a cyclic peptide (CSSTRESAC) that specifically binds to a vitamin D receptor, protein disulfide-isomerase A3 (PDIA3) expressed on the cell surface of tumor-associated macrophages (TAM), and targets breast cancer in syngeneic TNBC, non-TNBC xenograft, and transgenic mouse models. Systemic administration of CSSTRESAC to TNBC-bearing mice shifted the cytokine profile toward an antitumor immune response and delayed tumor growth. Moreover, CSSTRESAC enabled ligand-directed theranostic delivery to tumors and a mathematical model confirmed our experimental findings. Finally, in silico analysis showed PDIA3-expressing TAM in TNBC patients. This work uncovers a functional interplay between a cell surface vitamin D receptor in TAM and antitumor immune response that could be therapeutically exploited.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Medicine ; Mouse ; Triple-negative Breast Cancer ; Tumor-associated Macrophage ; Vitamin D Receptor; In-vivo; Structural Basis; Mouse Model; Expression; Peptide; Disparities; Mechanism; Delivery; Features; Complex
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Zeitschrift eLife
Quellenangaben Band: 10, Heft: , Seiten: , Artikelnummer: e65145 Supplement: ,
Verlag eLife Sciences Publications
Verlagsort Sheraton House, Castle Park, Cambridge, Cb3 0ax, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Metabolism and Cell Death (MCD)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-506900-001
Förderungen NCI NIH HHS
U.S. Department of Defense
U.S. Department of Energy
NIGMS NIH HHS
NIH HHS
National Science Foundation
DOI 10.7554/eLife.65145
WOS ID WOS:000658376100001
Scopus ID 85107449683
PubMed ID 34060472
Erfassungsdatum 2021-07-07
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