Skip to Main content Skip to Navigation
Journal articles

Characterization of Macrophages and Osteoclasts in the Osteosarcoma Tumor Microenvironment at Diagnosis: New Perspective for Osteosarcoma Treatment?

Anne Gomez-Brouchet 1 Julia Gilhodes 2 Nathalie van Acker 2 Regis Brion 3 Corinne Bouvier 4 Pauline Assemat 5 Nathalie Gaspar 6, 7, 8 Sébastien Aubert 9 Jean-Marc Guinebretiere 10 Béatrice Marie 11 Frederique Larousserie 12 Natacha Entz-Werlé 13 Gonzague de Pinieux Eric Mascard 8 François Gouin 14 Pierre Brousset 2 Marie-Dominique Tabone 15 Marta Jimenez 16 Marie-Cécile Le Deley 17 Jean-Yves Blay 18 Laurence Brugieres 8 Sophie Piperno-Neumann 10 Françoise Rédini 19
1 CRCT - Centre de Recherches en Cancérologie de Toulouse
2 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
3 INSERM U1238 - Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes]
4 TIMONE - Hôpital de la Timone [CHU - APHM]
5 IMFT - Institut de mécanique des fluides de Toulouse
6 IGR - Institut Gustave Roussy
7 Université Paris-Saclay
8 Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy]
9 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
10 Institut Curie [Paris]
11 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
12 CHU Cochin [AP-HP]
13 Hôpital de Hautepierre [Strasbourg]
14 UN Médecine - Université de Nantes - Faculté de médecine et des techniques médicales
15 AP-HP - Hôpital Armand Trousseau [AP-HP]
16 Centre Léon Bérard [Lyon]
17 Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France
18 Département cancer environnement (Centre Léon Bérard - Lyon)
19 University of Nantes, 44007 Nantes, France
Abstract : Biological and histopathological techniques identified osteoclasts and macrophages as targets of zoledronic acid (ZA), a therapeutic agent that was detrimental for patients in the French OS2006 trial. Conventional and multiplex immunohistochemistry of microenvironmental and OS cells were performed on biopsies of 124 OS2006 patients and 17 surgical (“OSNew”) biopsies respectively. CSF-1R (common osteoclast/macrophage progenitor) and TRAP (osteoclast activity) levels in serum of 108 patients were correlated to response to chemotherapy and to prognosis. TRAP levels at surgery and at the end of the protocol were significantly lower in ZA+ than ZA− patients (p adj = 0.0011; 0.0132). For ZA+-patients, an increase in the CSF-1R level between diagnosis and surgery and a high TRAP level in the serum at biopsy were associated with a better response to chemotherapy (p = 0.0091; p = 0.0251). At diagnosis, high CD163+ was associated with good prognosis, while low TRAP activity was associated with better overall survival in ZA− patients only. Multiplex immunohistochemistry demonstrated remarkable bipotent CD68+/CD163+ macrophages, homogeneously distributed throughout OS regions, aside osteoclasts (CD68+/CD163−) mostly residing in osteolytic territories and osteoid-matrix-associated CD68−/CD163+ macrophages. We demonstrate that ZA not only acts on harmful osteoclasts but also on protective macrophages, and hypothesize that the bipotent CD68+/CD163+ macrophages might present novel therapeutic targets.
Keywords : Osteosarcoma Zoledronic acid Osteoclast Macrophage Bipotent macrophage Multiplex
Document type :
Journal articles
Complete list of metadata
https://hal.archives-ouvertes.fr/hal-03141387
Contributor : Open Archive Toulouse Archive Ouverte (oatao) <>
Submitted on : Monday, February 15, 2021 - 11:31:12 AM
Last modification on : Tuesday, March 2, 2021 - 9:48:22 AM

File

Vignette du document
gomez-brouchet_27360.pdf
Publisher files allowed on an open archive

Identifiers

Collections

UNIV-TLSE3 | CURIE | PSL | FNCLCC | PHY-OS | UNIV-NANTES | CNRS | IMFT | IGR

Citation

Anne Gomez-Brouchet, Julia Gilhodes, Nathalie van Acker, Regis Brion, Corinne Bouvier, et al.. Characterization of Macrophages and Osteoclasts in the Osteosarcoma Tumor Microenvironment at Diagnosis: New Perspective for Osteosarcoma Treatment?. Cancers, MDPI, 2021, 13 (3), pp.13030423. ⟨10.3390/cancers13030423⟩. ⟨hal-03141387⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

93

Files downloads

48