---
_id: '10536'
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.
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.
article_number: '765151'
article_processing_charge: No
article_type: original
author:
- first_name: Cristina
  full_name: Stefanescu, Cristina
  last_name: Stefanescu
- first_name: Merel
  full_name: Van Gogh, Merel
  last_name: Van Gogh
- first_name: Marko
  full_name: Roblek, Marko
  id: 3047D808-F248-11E8-B48F-1D18A9856A87
  last_name: Roblek
  orcid: 0000-0001-9588-1389
- first_name: Mathias
  full_name: Heikenwalder, Mathias
  last_name: Heikenwalder
- first_name: Lubor
  full_name: Borsig, Lubor
  last_name: Borsig
citation:
  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>
  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>.
  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.
  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.
  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>.
  short: C. Stefanescu, M. Van Gogh, M. Roblek, M. Heikenwalder, L. Borsig, Frontiers
    in Oncology 11 (2021).
date_created: 2021-12-12T23:01:27Z
date_published: 2021-11-18T00:00:00Z
date_updated: 2023-08-17T06:20:32Z
day: '18'
ddc:
- '610'
department:
- _id: DaSi
doi: 10.3389/fonc.2021.765151
external_id:
  isi:
  - '000726603400001'
  pmid:
  - '34868988'
file:
- access_level: open_access
  checksum: 56cbac80e6891ce750511a30161b7792
  content_type: application/pdf
  creator: alisjak
  date_created: 2021-12-13T13:32:37Z
  date_updated: 2021-12-13T13:32:37Z
  file_id: '10539'
  file_name: 2021_Frontiers_Stefanescu.pdf
  file_size: 9245199
  relation: main_file
  success: 1
file_date_updated: 2021-12-13T13:32:37Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Oncology
publication_identifier:
  eissn:
  - 2234-943X
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: TGFβ signaling in myeloid cells promotes lung and liver metastasis through
  different mechanisms
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2021'
...