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.
Movassagh
Mojgan
M
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.
Spatz
Alain
A
Davoust
Jean
J
Lebecque
Serge
S
Romero
Pedro
P
Pittet
Mikaël
M
Rimoldi
Donata
D
Liénard
Danièle
D
Gugerli
Oliver
O
Ferradini
Laurent
L
Robert
Caroline
C
Avril
Marie-Françoise
MF
Zitvogel
Laurence
L
Angevin
Eric
E
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*
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