Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA.
Mod Pathol. 2012 Jul;25(7):1000-10. doi: 10.1038/modpathol.2012.43. Epub 2012 Mar 16.
The sentinel lymph node is the initial site of metastasis. Downregulation of antitumor immunity has a role in nodal progression. Our objective was to investigate the relationship between immune modulation and sentinel lymph node positivity, correlating it with outcome in melanoma patients. Lymph node/primary tissues from melanoma patients prospectively accrued and followed at New York University Medical Center were evaluated for the presence of regulatory T cells (Foxp3(+)) and dendritic cells (conventional: CD11c(+), mature: CD86(+)) using immunohistochemistry. Primary melanoma immune cell profiles from sentinel lymph node-positive/-negative patients were compared. Logistic regression models inclusive of standard-of-care/immunological primary tumor characteristics were constructed to predict the risk of sentinel lymph node positivity. Immunological responses in the positive sentinel lymph node were also compared with those in the negative non-sentinel node from the same nodal basin and matched negative sentinel lymph node. Decreased immune response was defined as increased regulatory T cells or decreased dendritic cells. Associations between the expression of these immune modulators, clinicopathological variables, and clinical outcome were evaluated using univariate/multivariate analyses. Primary tumor conventional dendritic cells and regression were protective against sentinel lymph node metastasis (odds ratio=0.714, 0.067; P=0.0099, 0.0816, respectively). Antitumor immunity was downregulated in the positive sentinel lymph node with an increase in regulatory T cells compared with the negative non-sentinel node from the same nodal basin (P=0.0005) and matched negative sentinel lymph node (P=0.0002). The positive sentinel lymph node also had decreased numbers of conventional dendritic cells compared with the negative sentinel lymph node (P<0.0001). Adding sentinel lymph node regulatory T cell expression improved the discriminative power of a recurrence risk assessment model using clinical stage. Primary tumor regression was associated with prolonged disease-free (P=0.025) and melanoma-specific (P=0.014) survival. Our results support an assessment of local immune profiles in both the primary tumor and sentinel lymph node to help guide therapeutic decisions.
前哨淋巴结是转移的初始部位。抗肿瘤免疫的下调在淋巴结进展中起作用。我们的目的是研究免疫调节与前哨淋巴结阳性之间的关系，并将其与黑色素瘤患者的预后相关联。前瞻性地从纽约大学医学中心采集并随访黑色素瘤患者的淋巴结/原发性组织，并用免疫组化法评估调节性 T 细胞（Foxp3(+））和树突状细胞（常规：CD11c(+），成熟：CD86(+））的存在情况。比较前哨淋巴结阳性/阴性患者的原发性黑色素瘤免疫细胞特征。构建包含标准治疗/免疫原发性肿瘤特征的逻辑回归模型，以预测前哨淋巴结阳性的风险。还比较了阳性前哨淋巴结中的免疫反应与同一淋巴结盆中的阴性非前哨淋巴结和匹配的阴性前哨淋巴结中的免疫反应。免疫反应的减少定义为调节性 T 细胞增加或树突状细胞减少。使用单变量/多变量分析评估这些免疫调节剂的表达与临床病理变量和临床结果之间的关系。原发性肿瘤常规树突状细胞和消退是前哨淋巴结转移的保护因素（比值比=0.714，0.067；P=0.0099，0.0816，分别）。与同一淋巴结盆中的阴性非前哨淋巴结（P=0.0005）和匹配的阴性前哨淋巴结（P=0.0002）相比，阳性前哨淋巴结中的抗肿瘤免疫被下调，表现为调节性 T 细胞增加。与阴性前哨淋巴结相比，阳性前哨淋巴结中的常规树突状细胞数量也减少（P<0.0001）。增加前哨淋巴结调节性 T 细胞的表达提高了使用临床分期进行复发风险评估模型的判别能力。原发性肿瘤消退与无病生存期延长（P=0.025）和黑色素瘤特异性生存期延长（P=0.014）相关。我们的结果支持对原发性肿瘤和前哨淋巴结中的局部免疫谱进行评估，以帮助指导治疗决策。
