Slan+ monocytes and macrophages mediate CD20-dependent b-cell lymphoma elimination via ADCC and ADCP

William Vermi, Alessandra Micheletti, Giulia Finotti, Cristina Tecchio, Federica Calzetti, Sara Costa, Mattia Bugatti, Stefano Calza, Claudio Agostinelli, Stefano Pileri, Piera Balzarini, Alessandra Tucci, Giuseppe Rossi, Lara Furlani, Giuseppe Todeschini, Alberto Zamó, Fabio Facchetti, Luisa Lorenzi, Silvia Lonardi, Marco A. Cassatella

Research output: Contribution to journalArticle

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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 FcgRs 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.

Original languageEnglish
Pages (from-to)3544-3559
Number of pages16
JournalCancer Research
Volume78
Issue number13
DOIs
Publication statusPublished - Jul 1 2018

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Antibody-Dependent Cell Cytotoxicity
Phagocytosis
Monocytes
Lymphoma
Macrophages
Lymphoma, Large B-Cell, Diffuse
Antibodies
Neoplasm Antibodies
Dendritic Cells
Neoplasms
Palatine Tonsil
Conditioned Culture Medium
Natural Killer Cells
Non-Hodgkin's Lymphoma
Lymph Nodes
Carcinoma
Phenotype

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Vermi, W., Micheletti, A., Finotti, G., Tecchio, C., Calzetti, F., Costa, S., ... Cassatella, M. A. (2018). Slan+ monocytes and macrophages mediate CD20-dependent b-cell lymphoma elimination via ADCC and ADCP. Cancer Research, 78(13), 3544-3559. https://doi.org/10.1158/0008-5472.CAN-17-2344

Slan+ monocytes and macrophages mediate CD20-dependent b-cell lymphoma elimination via ADCC and ADCP. / Vermi, William; Micheletti, Alessandra; Finotti, Giulia; Tecchio, Cristina; Calzetti, Federica; Costa, Sara; Bugatti, Mattia; Calza, Stefano; Agostinelli, Claudio; Pileri, Stefano; Balzarini, Piera; Tucci, Alessandra; Rossi, Giuseppe; Furlani, Lara; Todeschini, Giuseppe; Zamó, Alberto; Facchetti, Fabio; Lorenzi, Luisa; Lonardi, Silvia; Cassatella, Marco A.

In: Cancer Research, Vol. 78, No. 13, 01.07.2018, p. 3544-3559.

Research output: Contribution to journalArticle

Vermi, W, Micheletti, A, Finotti, G, Tecchio, C, Calzetti, F, Costa, S, Bugatti, M, Calza, S, Agostinelli, C, Pileri, S, Balzarini, P, Tucci, A, Rossi, G, Furlani, L, Todeschini, G, Zamó, A, Facchetti, F, Lorenzi, L, Lonardi, S & Cassatella, MA 2018, 'Slan+ monocytes and macrophages mediate CD20-dependent b-cell lymphoma elimination via ADCC and ADCP', Cancer Research, vol. 78, no. 13, pp. 3544-3559. https://doi.org/10.1158/0008-5472.CAN-17-2344
Vermi, William ; Micheletti, Alessandra ; Finotti, Giulia ; Tecchio, Cristina ; Calzetti, Federica ; Costa, Sara ; Bugatti, Mattia ; Calza, Stefano ; Agostinelli, Claudio ; Pileri, Stefano ; Balzarini, Piera ; Tucci, Alessandra ; Rossi, Giuseppe ; Furlani, Lara ; Todeschini, Giuseppe ; Zamó, Alberto ; Facchetti, Fabio ; Lorenzi, Luisa ; Lonardi, Silvia ; Cassatella, Marco A. / Slan+ monocytes and macrophages mediate CD20-dependent b-cell lymphoma elimination via ADCC and ADCP. In: Cancer Research. 2018 ; Vol. 78, No. 13. pp. 3544-3559.
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AU - Vermi, William

AU - Micheletti, Alessandra

AU - Finotti, Giulia

AU - Tecchio, Cristina

AU - Calzetti, Federica

AU - Costa, Sara

AU - Bugatti, Mattia

AU - Calza, Stefano

AU - Agostinelli, Claudio

AU - Pileri, Stefano

AU - Balzarini, Piera

AU - Tucci, Alessandra

AU - Rossi, Giuseppe

AU - Furlani, Lara

AU - Todeschini, Giuseppe

AU - Zamó, Alberto

AU - Facchetti, Fabio

AU - Lorenzi, Luisa

AU - Lonardi, Silvia

AU - Cassatella, Marco A.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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 FcgRs 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.

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