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Title: Distinctive subpopulations of stromal cells are present in human lymph nodes infiltrated with melanoma.
Austin Authors: Eom, Jennifer;Park, Saem Mul;Feisst, Vaughan;Chen, Chun-Jen J;Mathy, Joanna E;McIntosh, Julie D;Angel, Catherine E;Bartlett, Adam;Martin, Richard;Mathy, Jon A;Cebon, Jonathan S ;Black, Michael A;Brooks, Anna E S;Dunbar, P Rod
Affiliation: School of Biological Sciences, University of Auckland
Department of Surgery, Faculty of Medical Health Sciences, University of Auckland
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
La Trobe University School of Cancer Medicine, Heidelberg, Victoria, Australia
Department of Surgery, Waitemata District Health Board
Department of Surgery, Faculty of Medical Health Sciences, University of Auckland
Biochemistry, University of Otago
School of Biological Sciences, University of Auckland
Maurice Wilkins Centre & School of Biological Sciences, University of Auckland.
Issue Date: 24-Jun-2020 2020-06-24
Publication information: Cancer immunology research 2020; 8(8): 990-1003
Abstract: Metastasis of human tumors to lymph nodes (LNs) is a universally negative prognostic factor. LN stromal cells (SCs) play a crucial role in enabling T cell responses, and since tumor metastases modulate their structure and function, this interaction may suppress immune responses to tumor antigens. The SC subpopulations that respond to infiltration of malignant cells into human LNs have not been defined. Here, we identify distinctive subpopulations of CD90+ SCs present in melanoma-infiltrated LNs and compare them to their counterparts in normal LNs. The first population (CD90+ podoplanin+ CD105+ CD146+ CD271+ VCAM-1+ ICAM-1+ α-SMA+) corresponds to fibroblastic reticular cells (FRCs) that express various T cell modulating cytokines, chemokines and adhesion molecules. The second (CD90+ CD34+ CD105+ CD271+) represents a novel population of CD34+ SCs embedded in collagenous structures, such as the capsule and trabeculae, that predominantly produce extracellular matrix (ECM). We also demonstrated that these two SC subpopulations are distinct from two subsets of human LN pericytes- CD90+ CD146+ CD36+ NG2- pericytes in the walls of high endothelial venules and other small vessels, and CD90+ CD146+ NG2+ CD36- pericytes in the walls of larger vessels. Distinguishing between these CD90+ SC subpopulations in human LNs allows for further study of their respective impact on T cell responses to tumor antigens and clinical outcomes.
DOI: 10.1158/2326-6066.CIR-19-0796
ORCID: 0000-0002-2002-0194
PubMed URL: 32580941
Type: Journal Article
Appears in Collections:Journal articles

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