Osteoblasts remotely supply lung tumors with cancer-promoting SiglecF high neutrophils
Camilla Engblom
(1, 2)
,
Christina Pfirschke
(1, 2)
,
Rapolas Zilionis
(1, 3)
,
Janaina da Silva Martins
(1, 2)
,
Stijn Bos
(2)
,
Gabriel Courties
(1, 2)
,
Steffen Rickelt
(4)
,
Nicolas Severe
(2)
,
Ninib Baryawno
(2)
,
Julien Faget
(5, 6, 7)
,
Virginia Savova
(1)
,
David Zemmour
(1)
,
Jaclyn Kline
(1, 2)
,
Marie Siwicki
(1, 2)
,
Christopher Garris
(1, 2)
,
Ferdinando Pucci
(1, 2)
,
Hsin-Wei Liao
(1, 2)
,
Yi-Jang Lin
(1, 2)
,
Andita Newton
(1, 2)
,
Omar Yaghi
(1, 2)
,
Yoshiko Iwamoto
(1, 2)
,
Benoit Tricot
(1, 2)
,
Gregory Wojtkiewicz
(1, 2)
,
Matthias Nahrendorf
(1, 2)
,
Virna Cortez-Retamozo
(1, 2)
,
Etienne Meylan
(5, 6)
,
Richard Hynes
(4)
,
Marie Demay
(1, 2)
,
Allon Klein
(1)
,
Miriam Bredella
(2)
,
David Scadden
(2)
,
Ralph Weissleder
(1, 2)
,
Mikael Pittet
(1, 2)
1
HMS -
Harvard Medical School [Boston]
2 Massachusetts General Hospital [Boston]
3 Vilnius University [Vilnius]
4 MIT - Massachusetts Institute of Technology
5 ISREC - Swiss Institute for Experimental Cancer Research - Lausanne
6 EPFL - Ecole Polytechnique Fédérale de Lausanne
7 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
2 Massachusetts General Hospital [Boston]
3 Vilnius University [Vilnius]
4 MIT - Massachusetts Institute of Technology
5 ISREC - Swiss Institute for Experimental Cancer Research - Lausanne
6 EPFL - Ecole Polytechnique Fédérale de Lausanne
7 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
Julien Faget
- Fonction : Auteur
- PersonId : 766728
- ORCID : 0000-0003-0848-7135
Omar Yaghi
- Fonction : Auteur
- PersonId : 794487
- ORCID : 0000-0002-5611-3325
- IdRef : 244829365
Etienne Meylan
- Fonction : Auteur
- PersonId : 1062352
Mikael Pittet
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 1063168
Connectez-vous pour contacter l'auteur
Résumé
Bone marrow-derived myeloid cells can accumulate within tumors and foster cancer outgrowth. Local immune-neoplastic interactions have been intensively investigated, but the contribution of the systemic host environment to tumor growth remains poorly understood. Here, we show in mice and cancer patients (n = 70) that lung adenocarcinomas increase bone stromal activity in the absence of bone metastasis. Animal studies reveal that the cancer-induced bone phenotype involves bone-resident osteocalcin-expressing (Ocn+) osteoblastic cells. These cells promote cancer by remotely supplying a distinct subset of tumor-infiltrating SiglecFhigh neutrophils, which exhibit cancer-promoting properties. Experimentally reducing Ocn+ cell numbers suppresses the neutrophil response and lung tumor outgrowth. These observations posit osteoblasts as remote regulators of lung cancer and identify SiglecFhigh neutrophils as myeloid cell effectors of the osteoblast-driven protumoral response.