T-cell infiltration into the metastatic
melanoma microenvironment (
MME) correlates with improved patient survival. However, diffuse infiltration into
tumor occurs in only 8% of
melanoma metastases. Little is known about mechanisms governing T-cell infiltration into human
melanoma metastases or about how those mechanisms may be altered therapeutically. We hypothesized that T cells in the
MME would be enriched for
chemokine receptors CCR4, CCR5, CXCR3 and homing receptors relevant to the tissue site. Viably cryopreserved single cell
suspensions from nineteen
melanoma metastases representing three metastatic sites (
tumor-infiltrated lymph node, skin and small bowel) were evaluated by multiparameter flow cytometry and compared to benign lymph nodes and peripheral blood mononuclear cells from patients with Stage IIB-IV
melanoma. T cells in the
melanoma metastases contained large effector memory populations, high proportions of activated, moderately differentiated cells and few regulatory T cells. Site-specific homing was suggested in bowel, with high expression of CCR9. We neither encounter the anticipated enrichment of
integrin α4β7 in bowel, cutaneous leukocyte
antigen (CLA) in skin, nor
integrin α4β1 or
receptor CXCR3 in metastatic sites. Retention
integrins αEβ7, α1β1 and α2β1 were significantly elevated in
metastases. These data suggest limited tissue site-specific homing to human
melanoma metastases, but a significant role for retention
integrins in maintaining intratumoral T cells. Our findings also raise the possibility that T-cell homing, infiltration, and retention in
melanoma metastases may be increased by increasing expression of
ligands for CLA, α4β1 and CXCR3 on intratumoral endothelium.