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slan + Monocytes and Macrophages Mediate CD20-Dependent B-cell Lymphoma Elimination via ADCC and ADCP
Ist Teil von
Cancer research (Chicago, Ill.), 2018-07, Vol.78 (13), p.3544-3559
Ort / Verlag
United States: American Association for Cancer Research, Inc
Erscheinungsjahr
2018
Quelle
EZB-FREE-00999 freely available EZB journals
Beschreibungen/Notizen
Terminal tissue differentiation and function of slan
monocytes in cancer is largely unexplored. Our recent studies demonstrated that slan
monocytes differentiate into a distinct subset of dendritic cells (DC) in human tonsils and that slan
cells colonize metastatic carcinoma-draining lymph nodes. Herein, we report by retrospective analysis of multi-institutional cohorts that slan
cells infiltrate various types of non-Hodgkin lymphomas (NHL), particularly the diffuse large B-cell lymphoma (DLBCL) group, including the most aggressive, nodal and extranodal, forms. Nodal slan
cells displayed features of either immature DC or macrophages, in the latter case ingesting tumor cells and apoptotic bodies. We also found in patients with DLBCL that peripheral blood slan
monocytes, but not CD14
monocytes, increased in number and displayed highly efficient rituximab-mediated antibody-dependent cellular cytotoxicity, almost equivalent to that exerted by NK cells. Notably, slan
monocytes cultured in conditioned medium from nodal DLBCL (DCM) acquired a macrophage-like phenotype, retained CD16 expression, and became very efficient in rituximab-mediated antibody-dependent cellular phagocytosis (ADCP). Macrophages derived from DCM-treated CD14
monocytes performed very efficient rituximab-mediated ADCP, however, using different FcγRs from those used by slan
macrophages. Our observations shed new light on the complexity of the immune microenvironment of DLBCL and demonstrate plasticity of slan
monocytes homing to cancer tissues. Altogether, data identify slan
monocytes and macrophages as prominent effectors of antibody-mediated tumor cell targeting in patients with DLBCL.
slan
monocytes differentiate into macrophages that function as prominent effectors of antibody-mediated tumor cell targeting in lymphoma.
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