Origins of tumor-associated macrophages and neutrophils
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 al...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| 格式: | 文件 |
| 语言: | en_US |
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National Academy of Sciences (U.S.)
2014
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| 在线阅读: | http://hdl.handle.net/1721.1/91050 https://orcid.org/0000-0001-5629-4798 |
| _version_ | 1826193956806852608 |
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| author | 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. Kotelianski, Victor E. Figueiredo, Jose Luiz Chen, John W. Anderson, Daniel Griffith Nahrendorf, Matthias Swirski, Filip K. Weissleder, Ralph Pittet, Mikael J. |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering 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. Kotelianski, Victor E. Figueiredo, Jose Luiz Chen, John W. Anderson, Daniel Griffith Nahrendorf, Matthias Swirski, Filip K. Weissleder, Ralph Pittet, Mikael J. |
| author_sort | Cortez-Retamozo, Virna |
| collection | MIT |
| description | 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[superscript +] Ly-6C[superscript hi] monocytic and CD11b[superscript +] Ly-6G[superscript 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. |
| first_indexed | 2024-09-23T09:47:56Z |
| format | Article |
| id | mit-1721.1/91050 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:47:56Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/910502022-09-30T16:54:56Z Origins of tumor-associated macrophages and neutrophils 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. Kotelianski, Victor E. Figueiredo, Jose Luiz Chen, John W. Anderson, Daniel Griffith Nahrendorf, Matthias Swirski, Filip K. Weissleder, Ralph Pittet, Mikael J. Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Anderson, Daniel Griffith 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[superscript +] Ly-6C[superscript hi] monocytic and CD11b[superscript +] Ly-6G[superscript 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. 2014-10-21T16:57:27Z 2014-10-21T16:57:27Z 2012-02 2011-08 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/91050 Cortez-Retamozo, V., M. Etzrodt, A. Newton, P. J. Rauch, A. Chudnovskiy, C. Berger, R. J. H. Ryan, et al. “Origins of Tumor-Associated Macrophages and Neutrophils.” Proceedings of the National Academy of Sciences 109, no. 7 (January 30, 2012): 2491–2496. https://orcid.org/0000-0001-5629-4798 en_US http://dx.doi.org/10.1073/pnas.1113744109 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | 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. Kotelianski, Victor E. Figueiredo, Jose Luiz Chen, John W. Anderson, Daniel Griffith Nahrendorf, Matthias Swirski, Filip K. Weissleder, Ralph Pittet, Mikael J. Origins of tumor-associated macrophages and neutrophils |
| title | Origins of tumor-associated macrophages and neutrophils |
| title_full | Origins of tumor-associated macrophages and neutrophils |
| title_fullStr | Origins of tumor-associated macrophages and neutrophils |
| title_full_unstemmed | Origins of tumor-associated macrophages and neutrophils |
| title_short | Origins of tumor-associated macrophages and neutrophils |
| title_sort | origins of tumor associated macrophages and neutrophils |
| url | http://hdl.handle.net/1721.1/91050 https://orcid.org/0000-0001-5629-4798 |
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