GARP mRNA; LRRC32; cancer; glycoprotein A repetitions predominant (GARP); lymph node; metastases; transforming growth factor beta 1 (TGF-β1); tumor microenvironment; Oncology; Cancer Research
Abstract :
[en] Several types of cancer spread through the lymphatic system via the sentinel lymph nodes (LNs). Such LN-draining primary tumors, modified by tumor factors, lead to the formation of a metastatic niche associated with an increased number of Foxp3+ regulatory T cells (Tregs). These cells are expected to contribute to the elaboration of an immune-suppressive environment. Activated Tregs express glycoprotein A repetitions predominant (GARP), which binds and presents latent transforming growth factor beta 1 (TGF-β1) at their surface. GARP is also expressed by other non-immune cell types poorly described in LNs. Here, we mapped GARP expression in non-immune cells in human and mouse metastatic LNs. The mining of available (human and murine) scRNA-Seq datasets revealed GARP expression by blood (BEC)/lymphatic (LEC) endothelial, fibroblastic, and perivascular cells. Consistently, through immunostaining and in situ RNA hybridization approaches, GARP was detected in and around blood and lymphatic vessels, in (αSMA+) fibroblasts, and in perivascular cells associated with an abundant matrix. Strikingly, GARP was detected in LECs forming the subcapsular sinus and high endothelial venules (HEVs), two vascular structures localized at the interface between LNs and the afferent lymphatic and blood vessels. Altogether, we here provide the first distribution maps for GARP in human and murine LNs.
Disciplines :
Oncology
Author, co-author :
Rouaud, Loïc ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Baudin, Louis ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Gautier, Marine ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire ; Université Côte d'Azur, CNRS UMR7275, IPMC, 06560 Valbonne, France
Van Meerbeeck, Pierre; de Duve Institute, UCLouvain, 1200 Brussels, Belgium
Feyereisen, Emilie ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Blacher, Silvia ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
van Baren, Nicolas ; de Duve Institute, UCLouvain, 1200 Brussels, Belgium
Kridelka, Frédéric ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie-Obstétrique
Lucas, Sophie; de Duve Institute, UCLouvain, 1200 Brussels, Belgium ; WELBIO Department, WEL Research Institute, Avenue Pasteur, 6, 1300 Wavre, Belgium
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire ; WELBIO Department, WEL Research Institute, Avenue Pasteur, 6, 1300 Wavre, Belgium
Language :
English
Title :
Spatial Distribution of Non-Immune Cells Expressing Glycoprotein A Repetitions Predominant in Human and Murine Metastatic Lymph Nodes.
EOS - The Excellence Of Science Program F.R.S.-FNRS - Fonds de la Recherche Scientifique Fondation contre le Cancer ULiège FSR - Université de Liège. Fonds spéciaux pour la recherche Fondation Léon Fredericq FWB - Wallonia-Brussels Federation Télévie
Funding text :
This research was funded by the FWO and F.R.S.-FNRS under the Excellence of Science programme (EOS No. 0.0037.22) and supported by grants from the Fonds de la Recherche Scientifique-FNRS (F.R.S.-FNRS, Belgium), the FNRS PDR-Télévie (7.8511.19, 7.6534.21 and 7.8508.21), the Fondation contre le Cancer (foundation of public interest, Belgium; grants 2020-107 for FK, 2022-181 for A.N.; 2020-079 for S.L.), the Fonds spéciaux de la Recherche (University of Liège), the Fondation Hospitalo Universitaire Léon Fredericq (FHULF, University of Liège), the Fondation Salus Sanguinis, the Walloon Region through the FRFS-WELBIO (WELBIO: Walloon Excellence in Life Sciences and Biotechnology, WEL Research Institute, avenue Pasteur, 6, 1300 Wavre, Belgium) strategic research programme (grant CR-2019A-02 and CR-2019A-02R), and the Wallonia-Brussels Federation (grant for Concerted Research Actions No. 19/23-21 “INovLYMPHATIC”). L.R. and P.V.M. were supported by FNRS-télévie grants.
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