Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis.
Cell Rep
; 15(9): 2000-11, 2016 05 31.
Article
em En
| MEDLINE
| ID: mdl-27210762
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Progressão da Doença
/
Macrófagos
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Anticorpos Antineoplásicos
/
Neoplasias
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article