Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis
Tumors are composed of multiple cell types besides the tumor cells themselves, including innate immune cells such as macrophages. Tumor-associated macrophages (TAMs) are a heterogeneous population of myeloid cells present in the tumor microenvironment (TME). Here, they contribute to immunosuppressio...
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doaj-cc3f009b26304544ac716a2b2776c5122020-11-25T01:30:15ZengElsevierCell Reports2211-12472016-05-011592000201110.1016/j.celrep.2016.04.084Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and MetastasisAnna-Maria Georgoudaki0Kajsa E. Prokopec1Vanessa F. Boura2Eva Hellqvist3Silke Sohn4Jeanette Östling5Rony Dahan6Robert A. Harris7Mattias Rantalainen8Daniel Klevebring9Malin Sund10Suzanne Egyhazi Brage11Jonas Fuxe12Charlotte Rolny13Fubin Li14Jeffrey V. Ravetch15Mikael C.I. Karlsson16Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17176 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17176 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17176 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17176 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17176 Stockholm, SwedenDepartment of Oncology and Pathology, Karolinska Institutet, 17176 Stockholm, SwedenLaboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USADepartment of Clinical Neuroscience, Karolinska Institutet and Centre for Molecular Medicine, Karolinska University Hospital, 17176 Stockholm, SwedenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17176 Stockholm, SwedenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17176 Stockholm, SwedenDepartment of Surgical and Perioperative Sciences, Umeå University, 90187 Umeå, SwedenDepartment of Oncology and Pathology, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, SwedenDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, 17176 Stockholm, SwedenDepartment of Oncology and Pathology, Karolinska Institutet, 17176 Stockholm, SwedenLaboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USALaboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USADepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17176 Stockholm, SwedenTumors are composed of multiple cell types besides the tumor cells themselves, including innate immune cells such as macrophages. Tumor-associated macrophages (TAMs) are a heterogeneous population of myeloid cells present in the tumor microenvironment (TME). Here, they contribute to immunosuppression, enabling the establishment and persistence of solid tumors as well as metastatic dissemination. We have found that the pattern recognition scavenger receptor MARCO defines a subtype of suppressive TAMs and is linked to clinical outcome. An anti-MARCO monoclonal antibody was developed, which induces anti-tumor activity in breast and colon carcinoma, as well as in melanoma models through reprogramming TAM populations to a pro-inflammatory phenotype and increasing tumor immunogenicity. This anti-tumor activity is dependent on the inhibitory Fc-receptor, FcγRIIB, and also enhances the efficacy of checkpoint therapy. These results demonstrate that immunotherapies using antibodies designed to modify myeloid cells of the TME represent a promising mode of cancer treatment.http://www.sciencedirect.com/science/article/pii/S2211124716305290 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna-Maria Georgoudaki Kajsa E. Prokopec Vanessa F. Boura Eva Hellqvist Silke Sohn Jeanette Östling Rony Dahan Robert A. Harris Mattias Rantalainen Daniel Klevebring Malin Sund Suzanne Egyhazi Brage Jonas Fuxe Charlotte Rolny Fubin Li Jeffrey V. Ravetch Mikael C.I. Karlsson |
spellingShingle |
Anna-Maria Georgoudaki Kajsa E. Prokopec Vanessa F. Boura Eva Hellqvist Silke Sohn Jeanette Östling Rony Dahan Robert A. Harris Mattias Rantalainen Daniel Klevebring Malin Sund Suzanne Egyhazi Brage Jonas Fuxe Charlotte Rolny Fubin Li Jeffrey V. Ravetch Mikael C.I. Karlsson Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis Cell Reports |
author_facet |
Anna-Maria Georgoudaki Kajsa E. Prokopec Vanessa F. Boura Eva Hellqvist Silke Sohn Jeanette Östling Rony Dahan Robert A. Harris Mattias Rantalainen Daniel Klevebring Malin Sund Suzanne Egyhazi Brage Jonas Fuxe Charlotte Rolny Fubin Li Jeffrey V. Ravetch Mikael C.I. Karlsson |
author_sort |
Anna-Maria Georgoudaki |
title |
Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis |
title_short |
Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis |
title_full |
Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis |
title_fullStr |
Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis |
title_full_unstemmed |
Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis |
title_sort |
reprogramming tumor-associated macrophages by antibody targeting inhibits cancer progression and metastasis |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-05-01 |
description |
Tumors are composed of multiple cell types besides the tumor cells themselves, including innate immune cells such as macrophages. Tumor-associated macrophages (TAMs) are a heterogeneous population of myeloid cells present in the tumor microenvironment (TME). Here, they contribute to immunosuppression, enabling the establishment and persistence of solid tumors as well as metastatic dissemination. We have found that the pattern recognition scavenger receptor MARCO defines a subtype of suppressive TAMs and is linked to clinical outcome. An anti-MARCO monoclonal antibody was developed, which induces anti-tumor activity in breast and colon carcinoma, as well as in melanoma models through reprogramming TAM populations to a pro-inflammatory phenotype and increasing tumor immunogenicity. This anti-tumor activity is dependent on the inhibitory Fc-receptor, FcγRIIB, and also enhances the efficacy of checkpoint therapy. These results demonstrate that immunotherapies using antibodies designed to modify myeloid cells of the TME represent a promising mode of cancer treatment. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124716305290 |
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