{"acknowledgement":"The authors acknowledge the assistance of the Laboratory Animal Services Center (LASC) – UZH, Center for Microscopy and Image Analysis, and the Flow Cytometry Center of the University of Zurich.","day":"18","quality_controlled":"1","intvolume":"        11","date_updated":"2023-08-17T06:20:32Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"status":"public","abstract":[{"lang":"eng","text":"TGFβ overexpression is commonly detected in cancer patients and correlates with poor prognosis and metastasis. Cancer progression is often associated with an enhanced recruitment of myeloid-derived cells to the tumor microenvironment. Here we show that functional TGFβ-signaling in myeloid cells is required for metastasis to the lungs and the liver. Myeloid-specific deletion of Tgfbr2 resulted in reduced spontaneous lung metastasis, which was associated with a reduction of proinflammatory cytokines in the metastatic microenvironment. Notably, CD8+ T cell depletion in myeloid-specific Tgfbr2-deficient mice rescued lung metastasis. Myeloid-specific Tgfbr2-deficiency resulted in reduced liver metastasis with an almost complete absence of myeloid cells within metastatic foci. On contrary, an accumulation of Tgfβ-responsive myeloid cells was associated with an increased recruitment of monocytes and granulocytes and higher proinflammatory cytokine levels in control mice. Monocytic cells isolated from metastatic livers of Tgfbr2-deficient mice showed increased polarization towards the M1 phenotype, Tnfα and Il-1β expression, reduced levels of M2 markers and reduced production of chemokines responsible for myeloid-cell recruitment. No significant differences in Tgfβ levels were observed at metastatic sites of any model. These data demonstrate that Tgfβ signaling in monocytic myeloid cells suppresses CD8+ T cell activity during lung metastasis, while these cells actively contribute to tumor growth during liver metastasis. Thus, myeloid cells modulate metastasis through different mechanisms in a tissue-specific manner."}],"article_type":"original","has_accepted_license":"1","external_id":{"isi":["000726603400001"],"pmid":["34868988"]},"volume":11,"isi":1,"pmid":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"DaSi"}],"file_date_updated":"2021-12-13T13:32:37Z","language":[{"iso":"eng"}],"author":[{"full_name":"Stefanescu, Cristina","first_name":"Cristina","last_name":"Stefanescu"},{"first_name":"Merel","full_name":"Van Gogh, Merel","last_name":"Van Gogh"},{"id":"3047D808-F248-11E8-B48F-1D18A9856A87","last_name":"Roblek","first_name":"Marko","orcid":"0000-0001-9588-1389","full_name":"Roblek, Marko"},{"last_name":"Heikenwalder","first_name":"Mathias","full_name":"Heikenwalder, Mathias"},{"last_name":"Borsig","full_name":"Borsig, Lubor","first_name":"Lubor"}],"ddc":["610"],"year":"2021","file":[{"content_type":"application/pdf","date_updated":"2021-12-13T13:32:37Z","file_name":"2021_Frontiers_Stefanescu.pdf","date_created":"2021-12-13T13:32:37Z","file_size":9245199,"relation":"main_file","success":1,"access_level":"open_access","file_id":"10539","checksum":"56cbac80e6891ce750511a30161b7792","creator":"alisjak"}],"article_processing_charge":"No","date_published":"2021-11-18T00:00:00Z","publication":"Frontiers in Oncology","article_number":"765151","date_created":"2021-12-12T23:01:27Z","oa_version":"Published Version","citation":{"ieee":"C. Stefanescu, M. Van Gogh, M. Roblek, M. Heikenwalder, and L. Borsig, “TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms,” <i>Frontiers in Oncology</i>, vol. 11. Frontiers, 2021.","mla":"Stefanescu, Cristina, et al. “TGFβ Signaling in Myeloid Cells Promotes Lung and Liver Metastasis through Different Mechanisms.” <i>Frontiers in Oncology</i>, vol. 11, 765151, Frontiers, 2021, doi:<a href=\"https://doi.org/10.3389/fonc.2021.765151\">10.3389/fonc.2021.765151</a>.","chicago":"Stefanescu, Cristina, Merel Van Gogh, Marko Roblek, Mathias Heikenwalder, and Lubor Borsig. “TGFβ Signaling in Myeloid Cells Promotes Lung and Liver Metastasis through Different Mechanisms.” <i>Frontiers in Oncology</i>. Frontiers, 2021. <a href=\"https://doi.org/10.3389/fonc.2021.765151\">https://doi.org/10.3389/fonc.2021.765151</a>.","ista":"Stefanescu C, Van Gogh M, Roblek M, Heikenwalder M, Borsig L. 2021. TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. Frontiers in Oncology. 11, 765151.","ama":"Stefanescu C, Van Gogh M, Roblek M, Heikenwalder M, Borsig L. TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. <i>Frontiers in Oncology</i>. 2021;11. doi:<a href=\"https://doi.org/10.3389/fonc.2021.765151\">10.3389/fonc.2021.765151</a>","apa":"Stefanescu, C., Van Gogh, M., Roblek, M., Heikenwalder, M., &#38; Borsig, L. (2021). TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. <i>Frontiers in Oncology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fonc.2021.765151\">https://doi.org/10.3389/fonc.2021.765151</a>","short":"C. Stefanescu, M. Van Gogh, M. Roblek, M. Heikenwalder, L. Borsig, Frontiers in Oncology 11 (2021)."},"type":"journal_article","_id":"10536","publication_identifier":{"eissn":["2234-943X"]},"doi":"10.3389/fonc.2021.765151","title":"TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms","month":"11","publication_status":"published","publisher":"Frontiers","scopus_import":"1","oa":1}