Search: WFRF:(Franzén Fredrik)
> (2020-2024) >
Remodeling of the L...
Remodeling of the Lymph Node High Endothelial Venules Reflects Tumor Invasiveness in Breast Cancer and is Associated with Dysregulation of Perivascular Stromal Cells
-
- Bekkhus, Tove (author)
- Uppsala universitet,Klinisk immunologi
-
- Martikainen, Teemu (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
-
- Olofsson, A. (author)
- Karolinska Institutet,Uppsala universitet,Institutionen för immunologi, genetik och patologi
-
show more...
-
- Franzén Boger, Mathias (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
-
- Vasiliu Bacovia, Daniel (author)
- Uppsala universitet,Klinisk och experimentell patologi
-
- Wärnberg, Fredrik (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery,Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Surg, S-41345 Gothenburg, Sweden.
-
- Ulvmar, Maria H. (author)
- Uppsala universitet,Klinisk immunologi
-
show less...
-
(creator_code:org_t)
- 2021-01-08
- 2021
- English.
-
In: Cancers. - : MDPI AG. - 2072-6694. ; 13:2
- Related links:
-
https://europepmc.or...
-
show more...
-
https://doi.org/10.3...
-
https://uu.diva-port... (primary) (Raw object)
-
https://gup.ub.gu.se...
-
https://doi.org/10.3...
-
https://urn.kb.se/re...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- Simple Summary Tumor draining lymph nodes (TDLNs) are the most common metastatic sites in human cancer but are also essential sites for induction of tumor immunity. How different types of primary tumors affect the anti-tumor immune response in the LNs is not fully understood. By analyzing biobank tissue from breast cancer patients, we demonstrate that invasive breast cancer induce dramatic pre-metastatic LN changes affecting the structure and function of the specialized LN vasculature and associated stromal cells, required for recruitment of T-lymphocytes into the LNs. These changes could not be seen in patients with non-invasive breast cancer and provide new insights of how invasive tumors can disrupt essential functions within the immune system. The data also shows promise of LN stromal and vascular changes as possible future biomarkers for prediction of disease progression in human cancer. The tumor-draining lymph nodes (TDLNs) are primary sites for induction of tumor immunity. They are also common sites of metastasis, suggesting that tumor-induced mechanisms can subvert anti-tumor immune responses and promote metastatic seeding. The high endothelial venules (HEVs) together with CCL21-expressing fibroblastic reticular cells (FRCs) are essential for lymphocyte recruitment into the LNs. We established multicolor antibody panels for evaluation of HEVs and FRCs in TDLNs from breast cancer (BC) patients. Our data show that patients with invasive BC display extensive structural and molecular remodeling of the HEVs, including vessel dilation, thinning of the endothelium and discontinuous expression of the HEV-marker PNAd. Remodeling of the HEVs was associated with dysregulation of CCL21 in perivascular FRCs and with accumulation of CCL21-saturated lymphocytes, which we link to loss of CCL21-binding heparan sulfate in FRCs. These changes were rare or absent in LNs from patients with non-invasive BC and cancer-free organ donors and were observed independent of nodal metastasis. Thus, pre-metastatic dysregulation of core stromal and vascular functions within TDLNs reflect the primary tumor invasiveness in BC. This adds to the understanding of cancer-induced perturbation of the immune response and opens for prospects of vascular and stromal changes in TDLNs as potential biomarkers.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- lymph node
- pre-metastatic changes
- CCL21
- high endothelial venule
- (HEV)
- T-lymphocytes
- heparan sulfate
- fibroblastic reticular cell
- (FRC)
- breast cancer
- metastasis
- Oncology
- lymph node
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
-
Cancers
(Search for host publication in LIBRIS)
To the university's database