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ResearchIn-Press PreviewOncology Open Access | 10.1172/JCI167826
1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Fuller, A. in: JCI | PubMed | Google Scholar
1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Song, H. in: JCI | PubMed | Google Scholar
1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Ciotti, G. in: JCI | PubMed | Google Scholar
1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Gonzalez, M. in: JCI | PubMed | Google Scholar |
1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Murazzi, I. in: JCI | PubMed | Google Scholar
1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Ntekoumes, D. in: JCI | PubMed | Google Scholar
1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Skuli, N. in: JCI | PubMed | Google Scholar
1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Weeraratna, A. in: JCI | PubMed | Google Scholar |
1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Find articles by Weber, K. in: JCI | PubMed | Google Scholar
1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Abra, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
2Department of Chemical and Biomolecular Engineering, The Institute for Nano, Johns Hopkins University, Baltimore, United States of America
3Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, United States of America
4Department of Microbiology, Center for Cellular Immunotherapies, Parker Ins, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
5Department of Biomedical Engineering, Duke University, Durham, United States of America
6Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
7Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, United States of America
8Department of Biochemistry and Molecular Biology, John Hopkins Bloomberg School of Public Health, Baltimore, United States of America
9Penn Sarcoma Program, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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Published April 23, 2024 - More info
CD8+ T cell dysfunction impedes anti-tumor immunity in solid cancers but the underlying mechanisms are diverse and poorly understood. Extracellular matrix (ECM) composition has been linked to impaired T cell migration and enhanced tumor progression; however, impacts of individual ECM molecules on T cell function in the tumor microenvironment (TME) are only beginning to be elucidated. Upstream regulators of aberrant ECM deposition and organization in solid tumors are equally ill-defined. Therefore, we investigated how ECM composition modulates CD8+ T cell function in undifferentiated pleomorphic sarcoma (UPS), an immunologically active desmoplastic tumor. Using an autochthonous murine model of UPS and data from multiple human patient cohorts, we discovered a multifaceted mechanism wherein the transcriptional co-activator YAP1 promotes collagen VI (COLVI) deposition in the UPS TME. In turn, COLVI induces CD8+ T cell dysfunction and immune evasion by remodeling fibrillar collagen and inhibiting T cell autophagic flux. Unexpectedly, collagen I (COLI) opposed COLVI in this setting, promoting CD8+ T cell function and acting as a tumor suppressor. Thus, CD8+ T cell responses in sarcoma depend upon oncogene-mediated ECM composition and remodeling.