title: Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis.
abstract: 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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17176 Stockholm, Sweden.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Georgoudaki
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17176 Stockholm, Sweden.
authors.forename: Kajsa E
authors.initials: KE
authors.lastname: Prokopec
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17176 Stockholm, Sweden.
authors.forename: Vanessa F
authors.initials: VF
authors.lastname: Boura
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17176 Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Hellqvist
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17176 Stockholm, Sweden.
authors.forename: Silke
authors.initials: S
authors.lastname: Sohn
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet, 17176 Stockholm, Sweden.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Östling
authors.affiliation: Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Rony
authors.initials: R
authors.lastname: Dahan
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet and Centre for Molecular Medicine, Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harris
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17176 Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Rantalainen
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17176 Stockholm, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Klevebring
authors.affiliation: Department of Surgical and Perioperative Sciences, Umeå University, 90187 Umeå, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Suzanne Egyhazi
authors.initials: SE
authors.lastname: Brage
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17176 Stockholm, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Fuxe
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet, 17176 Stockholm, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rolny
authors.affiliation: Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USA; Shanghai Institute of Immunology and Hongqiao International Institute of Medicine, Faculty of Basic Medicine, School of Medicine, Shanghai Tongren Hospital, Shanghai Jiao Tong University, and Collaborative Innovation Center of Systems Biomedicine, Shanghai 200025, China.
authors.forename: Fubin
authors.initials: F
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Ravetch
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17176 Stockholm, Sweden. Electronic address: mikael.karlsson@ki.se.
authors.forename: Mikael C I
authors.initials: MC
authors.lastname: Karlsson
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D008264:Macrophages / Q000378:metabolism*; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D017452:Receptors, IgG / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D017154:Stromal Cells / Q000473:pathology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D016207:Cytokines; C080571:Fc gamma receptor IIB; C490460:MARCO protein, human; C092228:Marco protein, mouse; D017452:Receptors, IgG; D011971:Receptors, Immunologic