NDLI: Tumor-associated macrophages promote invasion while retaining Fc-dependent anti-tumor function.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nemeth, Jeffrey A. Harman, Benjamin C. Jordan, Robert E. Ekert, Jason E. Brezski, Randall J. Kinder, Michelle Strohl, William R. Anderson, G. Mark Greenplate, Allison R. McCabe, Francis L. Grugan, Katharine D. Van Rooijen, Nico
Description	Country affiliation: United States Author Affiliation: Grugan KD ( Biologics Research, Janssen Research & Development, Radnor, PA 19087, USA. kgrugan1@its.jnj.com)
Abstract	Tumor-associated macrophages (TAMs) have been shown to promote tumor progression, and increased TAM infiltration often correlates with poor prognosis. However, questions remain regarding the phenotype of macrophages within the tumor and their role in mAb-dependent cytotoxicity. This study demonstrates that whereas TAMs have protumor properties, they maintain Fc-dependent anti-tumor function. CD11b(+)CD14(+) TAMs isolated from primary human breast tumors expressed activating FcÎ³Rs. To model breast cancer TAMs in vitro, conditioned medium from breast cancer cells was used to drive human peripheral monocyte differentiation into macrophages. Tumor-conditioned macrophages were compared with in vitro derived M1 and M2a macrophages and were found to promote tumor cell invasion and express M2a markers, confirming their protumor potential. However, unlike M2a macrophages, tumor-conditioned macrophages expressed FcÎ³Rs and phagocytosed tumor cells in the presence of a tumor Ag-targeting mAb, unmasking an underappreciated tumoricidal capacity of TAMs. In vivo macrophage depletion reduced the efficacy of anti-CD142 against MDA-MB-231 xenograft growth and metastasis in SCID/beige mice, implicating a critical role for macrophages in Fc-dependent cell killing. M-CSF was identified in tumor-conditioned media and shown to be capable of differentiating macrophages with both pro- and anti-tumor properties. These results highlight the plasticity of TAMs, which are capable of promoting tumor progression and invasion while still retaining tumoricidal function in the presence of tumor-targeting mAbs.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	11
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antibodies, Neoplasm Immunology Antigens, Neoplasm Breast Neoplasms Macrophages Phagocytosis Receptors, Igg Animals Antigens, Cd11b Antigens, Cd14 Pathology Cell Movement Drug Effects Cell Proliferation Culture Media, Conditioned Pharmacology Disease Progression Immunophenotyping Macrophage Colony-stimulating Factor Mice Mice, Scid Neoplasm Invasiveness Neoplasm Transplantation Primary Cell Culture Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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