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- Jessica R. Ingram
- Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142;
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- Olga S. Blomberg
- Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142;
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- Jonathan T. Sockolosky
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305;
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- Lestat Ali
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115;
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- Florian I. Schmidt
- Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142;
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- Novalia Pishesha
- Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142;
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- Camilo Espinosa
- Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142;
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- Stephanie K. Dougan
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115;
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- K. Christopher Garcia
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305;
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- Hidde L. Ploegh
- Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142;
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- Michael Dougan
- Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142;
説明
<jats:title>Significance</jats:title> <jats:p>CD47 is a broadly expressed membrane-associated innate immune regulator that acts as a ligand of signal regulatory protein alpha (SIRPα) on antigen-presenting cells to inhibit phagocytosis. In xenograft models, inhibitors of the CD47–SIRPα interaction selectively target tumor-expressed CD47 and improve antibody responses to tumors by enhancing antibody-dependent cellular phagocytosis. In syngeneic settings, however, broad expression of CD47 on cells of the hematopoietic lineage creates a formidable antigen sink and increases toxicity. We find that optimal synergy between anti-CD47 antibodies and several immune therapies, including anti–CTLA-4, requires near-complete blockade of CD47 in the tumor microenvironment. Thus, novel strategies to deliver localized CD47 blockade to tumors may be particularly valuable for immune therapy.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 114 (38), 10184-10189, 2017-09-05
Proceedings of the National Academy of Sciences