eLife (Jun 2021)
Targeting a cell surface vitamin D receptor on tumor-associated macrophages in triple-negative breast cancer
- Fernanda I Staquicini,
- Amin Hajitou,
- Wouter HP Driessen,
- Bettina Proneth,
- Marina Cardó-Vila,
- Daniela I Staquicini,
- Christopher Markosian,
- Maria Hoh,
- Mauro Cortez,
- Anupama Hooda-Nehra,
- Mohammed Jaloudi,
- Israel T Silva,
- Jaqueline Buttura,
- Diana N Nunes,
- Emmanuel Dias-Neto,
- Bedrich Eckhardt,
- Javier Ruiz-Ramírez,
- Prashant Dogra,
- Zhihui Wang,
- Vittorio Cristini,
- Martin Trepel,
- Robin Anderson,
- Richard L Sidman,
- Juri G Gelovani,
- Massimo Cristofanilli,
- Gabriel N Hortobagyi,
- Zaver M Bhujwalla,
- Stephen K Burley,
- Wadih Arap,
- Renata Pasqualini
Affiliations
- Fernanda I Staquicini
- ORCiD
- 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
- Amin Hajitou
- Phage Therapy Group, Department of Brain Sciences, Imperial College London, London, United Kingdom
- Wouter HP Driessen
- The University of Texas M.D. Anderson Cancer Center, Houston, United States
- Bettina Proneth
- Institute of Metabolism and Cell Death, Helmholtz Zentrum Muenchen, Neuherberg, Germany
- Marina Cardó-Vila
- 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
- Daniela I Staquicini
- 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
- Christopher Markosian
- 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
- Maria Hoh
- 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
- Mauro Cortez
- ORCiD
- Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Anupama Hooda-Nehra
- Rutgers Cancer Institute of New Jersey, Newark, United States; Division of Hematology/Oncology, Department of Medicine, Rutgers New Jersey Medical School, Newark, United States
- Mohammed Jaloudi
- Rutgers Cancer Institute of New Jersey, Newark, United States; Division of Hematology/Oncology, Department of Medicine, Rutgers New Jersey Medical School, Newark, United States
- Israel T Silva
- Laboratory of Computational Biology, A.C. Camargo Cancer Center, São Paulo, Brazil
- Jaqueline Buttura
- Laboratory of Computational Biology, A.C. Camargo Cancer Center, São Paulo, Brazil
- Diana N Nunes
- Laboratory of Medical Genomics, A.C. Camargo Cancer Center, São Paulo, Brazil
- Emmanuel Dias-Neto
- Laboratory of Computational Biology, A.C. Camargo Cancer Center, São Paulo, Brazil; Laboratory of Medical Genomics, A.C. Camargo Cancer Center, São Paulo, Brazil
- Bedrich Eckhardt
- Translational Breast Cancer Program, Olivia Newton-John Cancer Research Institute, Melbourne, Australia
- Javier Ruiz-Ramírez
- Mathematics in Medicine Program, The Houston Methodist Research Institute, Houston, United States
- Prashant Dogra
- Mathematics in Medicine Program, The Houston Methodist Research Institute, Houston, United States
- Zhihui Wang
- Mathematics in Medicine Program, The Houston Methodist Research Institute, Houston, United States
- Vittorio Cristini
- Mathematics in Medicine Program, The Houston Methodist Research Institute, Houston, United States
- Martin Trepel
- Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Oncology and Hematology, University Medical Center Augsburg, Augsburg, Germany
- Robin Anderson
- Translational Breast Cancer Program, Olivia Newton-John Cancer Research Institute, Melbourne, Australia
- Richard L Sidman
- Department of Neurology, Harvard Medical School, Boston, United States
- Juri G Gelovani
- 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
- Massimo Cristofanilli
- Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University Chicago, Chicago, United States
- Gabriel N Hortobagyi
- Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, United States
- Zaver M Bhujwalla
- 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
- Stephen K Burley
- 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
- Wadih Arap
- ORCiD
- Rutgers Cancer Institute of New Jersey, Newark, United States; Division of Hematology/Oncology, Department of Medicine, Rutgers New Jersey Medical School, Newark, United States
- Renata Pasqualini
- 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
- DOI
- https://doi.org/10.7554/eLife.65145
- Journal volume & issue
-
Vol. 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.
Keywords
