Mesenchymal contribution to recruitment, infiltration, and positioning of leukocytes in human melanoma tissues.

To understand factors that regulate leukocyte entry and positioning within human melanoma tissues, we performed a multiparametric quantitative analysis of two separated regions: the intratumoral area and the peritumoral stroma. Using two mesenchymal markers, fibroblast activation protein (FAP) and CD90, we identified three subsets of mesenchymal cells (MCs): (i) intratumoral FAP(+)CD90(low/-) MC, (ii) peritumoral FAP(+)CD90(+) MC, and (iii) FAP(-)CD90(+) perivascular MC. We characterized CD90(+) MCs, which showed a stable CCL2-secretory phenotype when long-term expanded ex vivo, and heavily surrounded peritumoral Duffy antigen receptor for chemokine(+) (DARC) postcapillary venules, supporting a role for these vessels in peritumoral inflammatory leukocyte recruitment.