Abstract :
[en] The lymphatic system and the sentinel lymph node (SLN) are a spreading relay
for cancer cells in several cancer types, such as breast, cervical, head and neck, and
pancreatic carcinomas, as well as melanomas. Before metastatic colonization, the tumor-
draining LN undergoes remodeling, forming a pre-metastatic niche (PMN) associated
with an increased number of Foxp3+ regulatory T cells (Tregs). These modifications lead
to the creation of an immune-suppressive microenvironment. One of the factors leading
to immunosuppression is the transforming growth factor beta 1 (TGF-β1), secreted or
bound at the cell surface to a transmembrane receptor known as glycoprotein A
repetitions predominant (GARP). Several immune and non-immune cells are known to
express GARP, and Tregs are the best studied GARP+ cells. Non-immune cells are known
to play a significant role in the structure, organization, and function of LN. The cellular
sources and the spatial distribution of GARP in LNs during the metastatic process have
not been studied extensively. Through data mining of scRNA-Seq datasets of human and
mouse LNs, we revealed GARP expression in blood (BEC) and 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 the ECM. GARP was also detected in LECs forming
the subcapsular sinus and in high endothelial venules (HEVs), two vascular structures
localized at the interface between LNs and the afferent lymphatic and blood vessels,
respectively. Altogether, we provide the first report about the spatial distribution of non-
immune cells expressing GARP in human and murine metastatic LNs. These results
suggest a role for these cell populations in the immunosuppressive microenvironment in
the LN and open new perspectives for studying the secretion of active TGF-β1 by these
cells.
