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Long-Term Protective Effect of Mature DC-LAMP⁺ Dendritic Cell Accumulation in Sentinel Lymph Nodes Containing Micrometastatic Melanoma

Authors' Affiliations: ¹ Royal Surrey County Hospital Guildford, Guildford, United Kingdom; ² St George's University of London, London, United Kingdom; ³ Royal Prince Alfred Hospital, and ⁴ Wesmead Hospital, Sydney, Australia; ⁵ European Organization for Research and Treatment of Cancer Data Center, Brussels, Belgium; ⁶ Hospices Civils de Lyon, Université Lyon 1, Lyon, France; ⁷ Ludwig Institute for Cancer Research, Lausanne Branch, and ⁸ Lausanne University Hospital, Lausanne, Switzerland; ⁹ Charite Hospital, Berlin, Germany; ¹⁰ European Institute of Oncology, Milan, Italy; ¹¹ Erasmus Medical Center, Rotterdam, the Netherlands; ¹² Glasgow University Hospital, Glasgow, United Kingdom; and ¹³ Gustave-Roussy Institute, Villejuif, France

Requests for reprints: Alain Spatz, Department of BioPathology, Gustave Roussy Institute, 94805 Villejuif, France. Phone: 33-142-114-462; Fax: 33-142-115-263; E-mail: spatz{at}igr.fr.

Purpose: In a previous immunohistochemical study of dendritic cells (DC) in sentinel lymph nodes (SLN) draining regressing melanomas, we found that the accumulation of mature DC-LAMP⁺ DCs in SLNs was associated with local expansion of antigen-specific memory effector CTLs and the absence of metastasis in downstream lymph nodes. The aim of this study was to investigate the prognostic importance of the maximal density of mature DCs in SLNs.

Experimental Design: A total of 458 consecutive patients with micrometastatic melanoma within SLNs were eligible for analysis. The maximal density of mature DC-LAMP⁺ DCs was evaluated by three independent observers and categorized into three classes (<100, 100 to <200, and 200/mm²).

Results: There was excellent interobserver reproducibility for maximum density of mature DC-LAMP⁺ DC scores ( score = 0.82). There were differences in the maximal density scores and staining intensity according to the treating melanoma center (P < 0.001). The higher the mature DC density in the SLN is, the longer is the duration of survival [P = 0.047; hazard ratio, 0.70; 95% confidence interval, 0.50-1.00]. Adjusted by thickness and ulceration, the prognostic importance of DC density was lower (P = 0.36).

Conclusion: This study is the first to report the prognostic value of DC-LAMP⁺ DC counts in SLNs containing metastatic melanoma. Patients with a high density of mature DCs (200/mm²) have the lowest risk of death. It also provides evidence that a lack of maturation in the SLNs is important in biological facilitation of melanoma progression.

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