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Sentinel lymph nodes (SLNs), the initial site of regional metastases, directly receive lymph containing immune-modulatory cytokines and tumor cells from primary melanomas. Immune-suppressed SLNs are ideal for studies of tissue susceptibility to metastases. They show reduced antigen-presenting dendritic cells, activated T cells, high endothelial venules, and transvenular immigration of T cells. Tumor-induced immune suppression contributes to establishment of nodal metastases. SLNs may serve as an effective model to study reversal of tumor-induced immune suppression. We reviewed this topic in Nature Reviews of Immunology in 2006. We here summarize the Nature paper and provide additional results from ongoing studies and the recent literature.