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Selective accumulation of mature DC-Lamp+ dendritic cells in tumor sites is associated with efficient T-cell-mediated antitumor response and control of metastatic dissemination in melanoma.
The clinical relevance of dendritic cells (DCs) at the tumor site remains a matter of debate concerning their role in the generation of effective antitumor immunity in human cancers. We performed a comprehensive immunohistochemical analysis using a panel of DC-specific antibodies on regressing tumor lesions and sentinel lymph nodes (SLNs) in melanoma patients. Here we show in a case report involving spontaneous regression of metastatic melanoma that the accumulation of DC-Lamp+ DCs, clustered with tumor cells and lymphocytes, is associated with local expansion of antigen-specific memory effector CTLs. These findings were extended in a series of 19 melanoma-positive SLNs and demonstrated a significant correlation between the density of DC-Lamp+ DC infiltrates in SLNs with the absence of metastasis in downstream lymph nodes. This study, albeit performed in a limited series of patients, points to a pivotal role of mature DCs in the local expansion of efficient antitumor T-cell-mediated immune responses at the initial sites of metastasis and may have important implications regarding the prognosis, staging, and immunotherapy of melanoma patients.
Adult, Antigens, CD/immunology, Antigens, Neoplasm, Dendritic Cells/immunology, Humans, Immunophenotyping, Ligands, Lymph Nodes/pathology, Lymphatic Metastasis, Lymphocytes, Tumor-Infiltrating, Lysosome-Associated Membrane Glycoproteins, MART-1 Antigen, Male, Melanoma/immunology, Melanoma/secondary, Neoplasm Proteins/metabolism, Receptors, CCR6, Receptors, CCR7, Receptors, Chemokine/metabolism, Sentinel Lymph Node Biopsy, Skin Neoplasms/immunology, Skin Neoplasms/pathology, T-Lymphocytes, Cytotoxic/immunology
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