Journal Article

Spatial Distribution of Non-Immune Cells Expressing Glycoprotein A Repetitions Predominant in Human and Murine Metastatic Lymph Nodes

van Baren, Nicolas, Baudin, Louis, Van Meerbeeck, Pierre, Rouaud, Loïc, Lucas, Sophie, Feyereisen, Emilie, Gautier-Isola, Marine, Blacher, Silvia, Kridelka, Frédéric, Noel, Agnes

2023

Overview

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.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: B cells / Blood vessels / cancer / Cancer Research / Cloning / Cytokines / Endothelial cells / Endothelium / Foxp3 protein / GARP mRNA / Gene expression / glycoprotein A repetitions predominant (GARP) / Glycoproteins / Human health sciences / Hybrid vehicles / Hybridization / Immunohistochemistry / Immunoregulation / Immunosuppression / Immunotherapy / LRRC32 / lymph node / Lymph nodes / Lymphatic system / Lymphocytes T / Metastases / Metastasis / Neomycin / Oncologie / Oncology / Principal components analysis / RNA / Sciences de la santé humaine / Sensory neurons / Spatial distribution / T cell receptors / T cells / transforming growth factor beta 1 (TGF-β1) / Transforming growth factor-b1 / Transforming growth factors / tumor microenvironment / Tumors