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

被引:81
作者
Movassagh, M
Spatz, A
Davoust, J
Lebecque, S
Romero, P
Pittet, M
Rimoldi, D
Liénard, D
Gugerli, O
Ferradini, L
Robert, C
Avril, MF
Zitvogel, L
Angevin, E
机构
[1] Inst Gustave Roussy, Dept Biol Clin, INSERM, ERM0208,Unite Immunol, F-94805 Villejuif, France
[2] Inst Gustave Roussy, Dept Pathol, Immunotherapy Unit, Dermatol Unit, F-94805 Villejuif, France
[3] Inst Pasteur, INSERM, U277, F-75724 Paris, France
[4] CHU Vaudois, Dept Pathol, CH-1011 Lausanne, Switzerland
[5] Ludwig Inst Canc Res, Lausanne Branch, Div Clin OncoImmunol, Lausanne, Switzerland
[6] Schering Plough Corp, SPRI, Lab Immunol Res, Dardilly, France
关键词
D O I
10.1158/0008-5472.CAN-03-2969
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2192 / 2198
页数:7
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