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- Georgoudaki, Anna-Maria, et al.
(författare)
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Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis
- 2016
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 15:9, s. 2000-2011
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Tidskriftsartikel (refereegranskat)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, Fc gamma RIIB, 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.
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| 2. |
- Prokopec, Kajsa E., et al.
(författare)
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Up Regulated Complement and Fc Receptors in Juvenile Idiopathic Arthritis and Correlation with Disease Phenotype
- 2012
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Ingår i: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 32:3, s. 540-550
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The progress in identifying immunological mechanisms in juvenile idiopathic arthritis (JIA) has partly been hampered by the fact that the disease is heterogeneous. Here we have investigated complement and Fc receptors, as part of the inflammatory process, in two subgroups of JIA.METHODS: Blood from 26 patients with oligoarticular or polyarticular course type JIA and 21 healthy age and sex-matched controls were investigated by FACS and immunoassays.RESULTS: Increased numbers of monocytes and augmented plasma levels of C-reactive protein, C3a and IgG were found in both JIA subgroups. However, only polyarticular patients exhibited increased expression of Fc gamma receptor (FcγR) II and III and complement receptor (CR) 1 on monocytes along with enhanced CR1 expression on B cells. A correlation was observed between degree of receptor expression and C3a levels in the patients.CONCLUSIONS: Complement and Fc receptors are up regulated in children with multiple joint involvements, thus highlighting these pathways in the pathogenesis of polyarticular JIA.
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