title: 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.
abstract: 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.
authors.affiliation: Immunology/Institut National de la Santé et de la Recherche Médicale ERM0208 and Immunotherapy Unit, Department of Pathology, Dermatology Unit, Institut Gustave-Roussy, 94805 Villejuif Cedex, France.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Movassagh
authors.forename: Alain
authors.initials: A
authors.lastname: Spatz
authors.forename: Jean
authors.initials: J
authors.lastname: Davoust
authors.forename: Serge
authors.initials: S
authors.lastname: Lebecque
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Mikaël
authors.initials: M
authors.lastname: Pittet
authors.forename: Donata
authors.initials: D
authors.lastname: Rimoldi
authors.forename: Danièle
authors.initials: D
authors.lastname: Liénard
authors.forename: Oliver
authors.initials: O
authors.lastname: Gugerli
authors.forename: Laurent
authors.initials: L
authors.lastname: Ferradini
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Eric
authors.initials: E
authors.lastname: Angevin
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008024:Ligands; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating; D051907:Lysosomal Membrane Proteins; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000556:secondary; D009363:Neoplasm Proteins / Q000378:metabolism; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C106311:CCR6 protein, human; C515370:CCR7 protein, human; D008024:Ligands; D051907:Lysosomal Membrane Proteins; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine