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Slan+monocytes and macrophages mediate CD20-dependent b-cell lymphoma elimination via ADCC and ADCP
- Publication Year :
- 2018
-
Abstract
- 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. Significance: slan+ monocytes differentiate into macrophages that function as prominent effectors of antibody-mediated tumor cell targeting in lymphoma. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3544/F1.large.jpg. Cancer Res; 78(13); 3544–59. ©2018 AACR.
- Subjects :
- 0301 basic medicine
Cancer Research
CD14
CD16
03 medical and health sciences
Antigen
immune system diseases
hemic and lymphatic diseases
lan+ -monocytes
medicine
B-cell lymphoma
Antibody-dependent cell-mediated cytotoxicity
CD20
lan+ -monocytes, DLBCL, macrophages, ADCC, ADCP
biology
Chemistry
ADCP
medicine.disease
macrophages
Lymphoma
030104 developmental biology
Oncology
Cell culture
DLBCL
Cancer research
biology.protein
ADCC
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....7d170ea018921e124c73aa6d401c090f