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

Cancer Res. 2018 Jul 1;78(13):3544-3559. doi: 10.1158/0008-5472.CAN-17-2344. Epub 2018 May 10.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Antibody-Dependent Cell Cytotoxicity / immunology*
  • Antigens, CD20 / immunology
  • Antigens, CD20 / metabolism
  • Antineoplastic Agents, Immunological / pharmacology*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Biopsy
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cytophagocytosis / drug effects*
  • Cytophagocytosis / immunology
  • Female
  • Humans
  • Leukocytes, Mononuclear
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / immunology
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Primary Cell Culture
  • Retrospective Studies
  • Rituximab / pharmacology
  • Rituximab / therapeutic use
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology
  • Tumor Suppressor Proteins / metabolism
  • Young Adult

Substances

  • Antigens, CD20
  • Antineoplastic Agents, Immunological
  • SECISBP2L protein, human
  • Tumor Suppressor Proteins
  • Rituximab