Abstract
Metastasis of human tumors to lymph nodes (LN) is a universally negative prognostic factor. LN stromal cells (SC) play a crucial role in enabling T-cell responses, and because 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 with their counterparts in normal LNs. The first population (CD90
podoplanin
CD105
CD146
CD271
VCAM-1
ICAM-1
α-SMA
) corresponds to fibroblastic reticular cells 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. 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.