Sentinel Lymph Node Ckemokine Microenvironment Modulated by Melanoma Metastasis

摘要

Primary melanoma tumor-draining lymph nodes (LNs) play a significant role in controlling regional metastasis. Chemokine receptors CXCR4 and CCR7 are expressed on immune cells, whereby their respective ligands are, CXCL12 and CCL21. We hypothesized that melanoma metastasis to the sentinel LN (SLN) suppresses chemokine production, creating a more favorable tumor microenvironment for metastasis. A quantitative real-time reverse transcription PCR (qRT) assay was used to assess CXCL12 and CCL21 expression in paraffin-embedded (PE) SLN from melanoma patients (n = 124). SLN metastases were diagnosed by hematoxylin and eosin (H&E) and immunohistochemistry (IHC), and classified as macrome-tastases (>2.0 mm) or micrometastases (< =2.0 mm). CXCL12 and CCL21 levels were significantly enhanced in SLN with micrometastases than in SLN with macrometastases (CXCL12, p = 0.02; CCL21, p = 0.006) or in SLN without metastasis (CXCL12, p = 0.04; CCL21, p< 0.001). IHC analysis of SLN showed that the chemokine mRNA expression correlated with protein expression. Increase in primary tumor burden significantly correlated with suppressed CXCL12 (p < 0.0001) and CCL21 (p<0.05) expression in the SLN. Progression of nodal metastasis burden and primary tumor burden was shown to significantly suppress both SLN CXCL12 and CCL21. Reversal of this chemokine suppression may improve the immunity of draining LN against tumor invasion.