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https://ahro.austin.org.au/austinjspui/handle/1/27811| Title: | Targeting a cell surface vitamin D receptor on tumor-associated macrophages in triple-negative breast cancer. | Austin Authors: | Staquicini, Fernanda I;Hajitou, Amin;Driessen, Wouter Hp;Proneth, Bettina;Cardó-Vila, Marina;Staquicini, Daniela I;Markosian, Christopher;Hoh, Maria;Cortez, Mauro;Hooda-Nehra, Anupama;Jaloudi, Mohammed;Silva, Israel T;Buttura, Jaqueline;Nunes, Diana N;Dias-Neto, Emmanuel;Eckhardt, Bedrich;Ruiz-Ramírez, Javier;Dogra, Prashant;Wang, Zhihui;Cristini, Vittorio;Trepel, Martin;Anderson, Robin L ;Sidman, Richard L;Gelovani, Juri G;Cristofanilli, Massimo;Hortobagyi, Gabriel N;Bhujwalla, Zaver M;Burley, Stephen K;Arap, Wadih;Pasqualini, Renata | Affiliation: | Department of Oncology and Hematology, University Medical Center Augsburg, Augsburg, Germany Olivia Newton-John Cancer Research Institute Department of Cellular and Molecular Medicine, The University of Arizona Cancer Center, University of Arizona, Tucson, United States Department of Otolaryngology-Head and Neck Surgery, The University of Arizona Cancer Center, University of Arizona, Tucson, United States Rutgers Cancer Institute of New Jersey, Newark, United States Division of Cancer Biology, Department of Radiation Oncology, Rutgers New Jersey Medical School, Newark, United States Division of Hematology/Oncology, Department of Medicine, Rutgers New Jersey Medical School, Newark, United States Laboratory of Computational Biology, A.C. Camargo Cancer Center, São Paulo, Brazil Laboratory of Medical Genomics, A.C. Camargo Cancer Center, São Paulo, Brazil Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Department of Biomedical Engineering, College of Engineering, Wayne State University, Detroit, United States Department of Oncology, School of Medicine, Wayne State University, Detroit, United States Department of Neurosurgery, School of Medicine, Wayne State University, Detroit, United States Rutgers Cancer Institute of New Jersey, New Brunswick, United States Research Collaboratory for Structural Bioinformatics Protein Data Bank, San Diego Supercomputer Center, University of California-San Diego, La Jolla, United States Research Collaboratory for Structural Bioinformatics Protein Data Bank, Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, United States Institute of Metabolism and Cell Death, Helmholtz Zentrum Muenchen, Neuherberg, Germany Phage Therapy Group, Department of Brain Sciences, Imperial College London, London, United Kingdom The University of Texas M.D. Anderson Cancer Center, Houston, United States Division of Cancer Imaging Research, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, United States Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil Laboratory of Computational Biology, A.C. Camargo Cancer Center, São Paulo, Brazil Laboratory of Medical Genomics, A.C. Camargo Cancer Center, São Paulo, Brazil Mathematics in Medicine Program, The Houston Methodist Research Institute, Houston, United States Department of Neurology, Harvard Medical School, Boston, United States Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University Chicago, Chicago, United States Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, United States Division of Cancer Imaging Research, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, United States |
Issue Date: | 1-Jul-2021 | Publication information: | eLife 2021; 10 | Abstract: | 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. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/27811 | DOI: | 10.7554/eLife.65145 | ORCID: | 0000-0003-1137-6575 0000-0001-6536-4647 0000-0002-8686-4584 |
Journal: | eLife | PubMed URL: | 34060472 | Type: | Journal Article | Subjects: | medicine mouse triple-negative breast cancer tumor-associated macrophage vitamin D receptor |
| Appears in Collections: | Journal articles |
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