slan+ Monocytes and Macrophages Mediate CD20-Dependent B-cell Lymphoma Elimination via ADCC and ADCP.
William VermiAlessandra MichelettiGiulia FinottiCristina TecchioFederica CalzettiSara CostaMattia BugattiStefano CalzaClaudio AgostinelliStefano PileriPiera BalzariniAlessandra TucciGiuseppe RossiLara FurlaniGiuseppe TodeschiniAlberto ZamòFabio FacchettiLuisa LorenziSilvia LonardiMarco A CassatellaPublished in: Cancer research (2018)
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.
Keyphrases
- diffuse large b cell lymphoma
- dendritic cells
- peripheral blood
- epstein barr virus
- induced apoptosis
- lymph node
- nk cells
- immune response
- papillary thyroid
- cell cycle arrest
- regulatory t cells
- small cell lung cancer
- single cell
- endothelial cells
- squamous cell carcinoma
- cell death
- radiation therapy
- poor prognosis
- stem cells
- squamous cell
- endoplasmic reticulum stress
- cancer therapy
- gene expression
- neoadjuvant chemotherapy
- signaling pathway
- drug delivery
- deep learning
- anti inflammatory
- young adults
- artificial intelligence
- induced pluripotent stem cells
- cross sectional