Long-term protective effect of mature DC-LAMP⁺ dendritic cell accumulation in sentinel lymph nodes containing micrometastatic melanoma. An EORTC Melanoma group study

8509 Background: In a previous immunohistochemical study of dendritic cells (DCs) in sentinel lymph nodes (SLNs) 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 cytotoxic T lymphocytes 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 using the anti-DC LAMP antibody. Methods: 458 consecutive patients with micrometastatic melanoma within SLNs and 3 yrs follow-up after SLN procedure or death within 3 yrs were eligible for analysis. Semi-quantitative evaluation of mature DC DC-LAMP+ maximum density was made as follows: the slide was examined at intermediate magnification (x100) to select the area containing the maximum number of DC-LAMP+ DCs, the number of DC-LAMP+ cells per mm 2 was then determined at high magnification (x400) in 3 mm 2 in high density areas. Results were reported as number of cells /mm2. The maximal density of mature DC-LAMP+ DCs was evaluated by three independent observers and categorized into three classes (<100/mm 2 , 100- <200/mm 2 , ≥200/mm 2 ) according to previously reported cutpoints. Results: There was excellent inter-observer reproducibility for maximum density of mature DC-LAMP+ DCs scores (kappa score = 0.82). There were differences in the maximal density scores and staining intensity according to the center (P<0.001). The higher the mature DC density in the SLN the longer the duration of survival [p=0.047; hazard ratio (95% CI) = 0.70 (0.50–1.00)]. Conclusions: 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/mm 2 ) have the lowest risk of death. It also provides evidence that a lack of DC maturation in the SLNs is important in biological facilitation of melanoma progression. No significant financial relationships to disclose.