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Brech, D. ; Herbstritt, A. ; Diederich, S. ; Straub, T.* ; Kokolakis, E. ; Irmler, M. ; Beckers, J. ; Büttner, F.A.* ; Schaeffeler, E.* ; Winter, S.* ; Nelson, P.J.* ; Nößner, E.

Dendritic cells or macrophages? The microenvironment of human clear cell renal cell carcinoma imprints a mosaic myeloid subtype associated with patient survival.

Cells 11:3289 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Since their initial description by Elie Metchnikoff, phagocytes have sparked interest in a variety of biologic disciplines. These important cells perform central functions in tissue repair and immune activation as well as tolerance. Myeloid cells can be immunoinhibitory, particularly in the tumor microenvironment, where their presence is generally associated with poor patient prognosis. These cells are highly adaptable and plastic, and can be modulated to perform desired functions such as antitumor activity, if key programming molecules can be identified. Human clear cell renal cell carcinoma (ccRCC) is considered immunogenic; yet checkpoint blockades that target T cell dysfunction have shown limited clinical efficacy, suggesting additional layers of immunoinhibition. We previously described “enriched-in-renal cell carcinoma” (erc) DCs that were often found in tight contact with dysfunctional T cells. Using transcriptional profiling and flow cytometry, we describe here that ercDCs represent a mosaic cell type within the macrophage continuum co-expressing M1 and M2 markers. The polarization state reflects tissue-specific signals that are characteristic of RCC and renal tissue homeostasis. ErcDCs are tissue-resident with increasing prevalence related to tumor grade. Accordingly, a high ercDC score predicted poor patient survival. Within the profile, therapeutic targets (VSIG4, NRP1, GPNMB) were identified with promise to improve immunotherapy.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Gene Expression ; Gpnmb ; Macrophage Plasticity ; Mononuclear Phagocyte System ; Nrp1 ; Tissue Macrophage ; Tumor Microenvironment ; Vsig4
ISSN (print) / ISBN 2073-4409
e-ISSN 2073-4409
Zeitschrift Cells
Quellenangaben Band: 11, Heft: 20, Seiten: , Artikelnummer: 3289 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Institut(e) CF Immunoanalytics (IMA)
Institute of Experimental Genetics (IEG)
Förderungen Deutsche Krebshilfe
Deutsche Forschungsgemeinschaft
Robert Bosch Stiftung
ICEPHA Graduate School Tuebingen-Stuttgart
Helmholtz Alliance