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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

¹ Immunology/Institut National de la Santé et de la Recherche Médicale ERM0208 and Immunotherapy Unit, Department of Pathology, Dermatology Unit, Institut Gustave-Roussy, Villejuif, France; ² Laboratory of Immunological Research, SPRI, Schering-Plough, Dardilly, France; ³ Division of Clinical OncoImmunology, Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Pathology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; ⁴ Institut National de la Santé et de la Recherche Médicale U277, Institut Pasteur, Paris, France

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.

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