Cytokine profiles of sentinel lymph nodes draining the primary melanoma

Background: The sentinel lymph node (SLN) draining the primary melanoma is the first echelon node where micrometastasis is established. SLNs may be the initial sites of antigen presentation associated with immune responses. Methods: A portion of each SLN from 68 melanoma patients undergoing selective SLN dissection was processed for enzyme-linked immunospot (ELISPOT) assay determination of interferon gamma (IFN-gamma), interleukin-2 (IL-2), granulocyte macrophage colony-stimulating factor (GM-CSF), and interleukin-10 (IL-10) secretion. The control was the adjacent non-SLN. Lymphocytes were stimulated with staphylococcal enterotoxin A (SEA) prior to ELISPOT assay. Results: No significant difference was noted in the production of IL-10 between the SLNs and non-SLNs. Significant production of IFN-gamma, IL-2, and GM-CSF was noted in the SLNs when compared to the non-SLNs in the overall group. Patients with no micrometastasis (n = 60) had elevated secretion of all cytokines in the SLNs. However, patients harboring lymph node micrometastasis (n = 8) showed no increase of cytokine secretion in the SLNs. Conclusions: Significant Th1 and Th2 response was induced in melanoma-free SLNs. Implications: SLNs without micrometastasis may be activated by submicroscopic cells or soluble tumor antigens, while cytokine production may be down-regulated by micrometastasis. Future studies should be directed towards identifying the specific SLN T cells recognizing the tumor antigens.