slan+ thorn Monocytes and Macrophages Mediate CD20-Dependent B-cell Lymphoma Elimination via ADCC and ADCP

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 Fc gamma Rs 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. (C) 2018 AACR.