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The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

Origins of tumor-associated macrophages and neutrophils

Open access
Cortez-Retamozo, Virna, Etzrodt, Martin, Newton, Andita, Rauch, Philipp J., Chudnovskiy, Aleksey, Berger, Cedric, Ryan, Russell J. H., Iwamoto, Yoshiko, Marinelli, Brett, Gorbatov, Rostic, Forghani, Reza, Novobrantseva, Tatiana I., Koteliansky, Victor, Figueiredo, Jose-Luiz, Chen, John W., Anderson, Daniel G., Nahrendorf, Matthias, Swirski, Filip K., Weissleder, Ralph, Pittet, Mikael J.·2012·Proceedings of the National Academy of Sciences

Abstract

Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) can control cancer growth and exist in almost all solid neoplasms. The cells are known to descend from immature monocytic and granulocytic cells, respectively, which are produced in the bone marrow. However, the spleen is also a recently identified reservoir of monocytes, which can play a significant role in the inflammatory response that follows acute injury. Here, we evaluated the role of the splenic reservoir in a genetic mouse model of lung adenocarcinoma driven by activation of oncogenic Kras and inactivation of p53. We found that high numbers of TAM and TAN precursors physically relocated from the spleen to the tumor stroma, and that recruitment of tumor-promoting spleen-derived TAMs required signaling of the chemokine receptor CCR2. Also, removal of the spleen, either before or after tumor initiation, reduced TAM and TAN responses significantly and delayed tumor growth. The mechanism by which the spleen was able to maintain its reservoir capacity throughout tumor progression involved, in part, local accumulation in the splenic red pulp of typically rare extramedullary hematopoietic stem and progenitor cells, notably granulocyte and macrophage progenitors, which produced CD11b + Ly-6C hi monocytic and CD11b + Ly-6G hi granulocytic cells locally. Splenic granulocyte and macrophage progenitors and their descendants were likewise identified in clinical specimens. The present study sheds light on the origins of TAMs and TANs, and positions the spleen as an important extramedullary site, which can continuously supply growing tumors with these cells.

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Metadata

Authors
Cortez-Retamozo, V., Etzrodt, M., Newton, A., Rauch, P. J., Chudnovskiy, A., Berger, C., Ryan, R. J. H., Iwamoto, Y., Marinelli, B., Gorbatov, R., Forghani, R., Novobrantseva, T. I., Koteliansky, V., Figueiredo, J.-L., Chen, J. W., Anderson, D. G., Nahrendorf, M., Swirski, F. K., Weissleder, R., & Pittet, M. J.
Venue
Proceedings of the National Academy of Sciences
Published
2012-01-30
Volume
109
Issue
7
Pages
2491-2496
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2158809810
Cited by
689
References
11
FWCI
18.98
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Origins of tumor-associated macrophages and neutrophils. https://app.cochat.ai/papers/10.1073/pnas.1113744109
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Cortez-Retamozo, V., Etzrodt, M., Newton, A., Rauch, P. J., Chudnovskiy, A., Berger, C., Ryan, R. J. H., Iwamoto, Y., Marinelli, B., Gorbatov, R., Forghani, R., Novobrantseva, T. I., Koteliansky, V., Figueiredo, J.-L., Chen, J. W., Anderson, D. G., Nahrendorf, M., Swirski, F. K., Weissleder, R., & Pittet, M. J. (2012). Origins of tumor-associated macrophages and neutrophils. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1113744109

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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