CD40 signaling instructs chronic lymphocytic leukemia cells to attract monocytes via the CCR2 axis
| Autor: | Jaco A. C. van Bruggen, Sabina Kersting, Martijn H. A. van Attekum, Arnon P. Kater, Erik Slinger, Emilie Reinen, Eric Eldering, M Cristina Lebre |
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| Přispěvatelé: | Other departments, CCA - Cancer biology and immunology, Experimental Immunology, Clinical Haematology |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Receptors CCR2 T-Lymphocytes Chronic lymphocytic leukemia CD40 Ligand Cell Communication Monocytes Article 03 medical and health sciences 0302 clinical medicine Cell Movement immune system diseases hemic and lymphatic diseases Tumor Microenvironment medicine Humans Macrophage Chronic Lymphocytic Leukemia CD40 Antigens Lymph node CD40 030102 biochemistry & molecular biology biology business.industry Monocyte ZAP70 Hematology medicine.disease Leukemia Lymphocytic Chronic B-Cell medicine.anatomical_structure Immunology biology.protein Cytokine secretion Chemokines CD5 business Signal Transduction 030215 immunology |
| Zdroj: | Haematologica Haematologica, 102(12), 2069-2076. Ferrata Storti Foundation |
| ISSN: | 0390-6078 |
| DOI: | 10.3324/haematol.2016.157206 |
| Popis: | Chronic lymphocytic leukemia (CLL) cells are provided with essential survival and proliferative signals in the lymph node microenvironment. Here, CLL cells engage in various interactions with bystander cells such as T cells and macrophages. Phenotypically distinct types of tumor infiltrating macrophages can either be tumor supportive (M2) or play a role in tumor immune surveillance (M1). Although recent in vitro findings suggest a protective role for macrophages in CLL, the actual balance between these macrophage subsets in CLL lymphoid tissue is still unclear. Furthermore, the mechanism of recruitment of monocytes towards the CLL lymph node is currently unknown. Both questions are addressed in this paper. Immunofluorescence staining of lymph node samples showed macrophage skewing towards an M2 tumor-promoting phenotype. This polarization likely results from CLL-secreted soluble factors, as both patient serum and CLL-conditioned medium recapitulated the skewing effect. Considering that CLL cell cytokine secretion is affected by adjacent T cells, we next studied CLL-mediated monocyte recruitment in the presence or absence of T-cell signals. While unstimulated CLL cells were inactive, T cell-stimulated CLL cells actively recruited monocytes. This correlated with secretion of various chemokines such as C-C-motif-ligand-2,3,4,5,7,24, C-X-C-motif-ligand-5,10, and Interleukin-10. We also identified CD40L as the responsible T-cell factor that mediated recruitment, and showed that recruitment critically depended on the C-C-motif-chemokine-receptor-2 axis. These studies show that the shaping of a tumor supportive microenvironment depends on cytokinome alterations (including C-C-motif-ligand-2) that occur after interactions between CLL, T cells and monocytes. Therefore, targeted inhibition of CD40L or C-C-motif-chemokine-receptor-2 may be relevant therapeutic options. |
| Databáze: | OpenAIRE |
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