Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neutrophils
Camilla Engblom,Christina Pfirschke,Rapolas Zilionis,Rapolas Zilionis,Janaina S. Martins,Stijn A. Bos,Gabriel Courties,Steffen Rickelt,Nicolas Severe,Ninib Baryawno,Julien Faget,Virginia Savova,David Zemmour,Jaclyn Kline,Marie Siwicki,Christopher Garris,Ferdinando Pucci,Hsin-Wei Liao,Yi Jang Lin,Andita Newton,Omar K. Yaghi,Yoshiko Iwamoto,Benoit Tricot,Gregory R. Wojtkiewicz,Matthias Nahrendorf,Virna Cortez-Retamozo,Etienne Meylan,Richard O. Hynes,Marie B. Demay,Allon M. Klein,Miriam A. Bredella,David T. Scadden,Ralph Weissleder,Mikael J. Pittet +33 more
TLDR
In this paper, the authors show that lung adenocarcinomas increase bone stromal activity in the absence of bone metastasis and identify osteoblasts as remote regulators of lung cancer and identify SiglecFhigh neutrophils as myeloid cell effectors of the osteoblast-driven protumoral response.Abstract:
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.read more
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Understanding the tumor immune microenvironment (TIME) for effective therapy.
Mikhail Binnewies,Edward W. Roberts,Kelly Kersten,Vincent Chan,Douglas F. Fearon,Miriam Merad,Lisa M. Coussens,Dmitry I. Gabrilovich,Suzanne Ostrand-Rosenberg,Suzanne Ostrand-Rosenberg,Catherine C. Hedrick,Robert H. Vonderheide,Mikael J. Pittet,Rakesh K. Jain,Weiping Zou,T. Kevin Howcroft,Elisa C. Woodhouse,Robert A. Weinberg,Matthew F. Krummel +18 more
TL;DR: By parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient’s tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed.
Journal ArticleDOI
Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species.
Rapolas Zilionis,Rapolas Zilionis,Camilla Engblom,Christina Pfirschke,Virginia Savova,David Zemmour,Hatice D. Saatcioglu,Indira Krishnan,Indira Krishnan,Giorgia Maroni,Giorgia Maroni,Giorgia Maroni,Claire V. Meyerovitz,Clara M. Kerwin,Sun Choi,William G. Richards,Assunta De Rienzo,Daniel G. Tenen,Daniel G. Tenen,Raphael Bueno,Elena Levantini,Elena Levantini,Elena Levantini,Mikael J. Pittet,Allon M. Klein +24 more
TL;DR: The lung TIM landscape is determined and sets the stage for future investigations into the potential of TIMs as immunotherapy targets by using single-cell RNA sequencing to map TIMs in non-small-cell lung cancer patients.
Journal ArticleDOI
Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
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TL;DR: The emerging dual role played by neutrophils in the tumour microenvironment is discussed, while also mediating antitumour immune responses, and it is suggested that neutrophil function could be manipulated in myeloid cell-based therapeutic approaches to improve patient outcomes.
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