Abstract Background: The prognosis for stage III melanoma is variable, with the 5-year survival ranging from 23-87%. Previous studies have demonstrated both immune cell activation and dysfunction within the sentinel lymph node (SLN) of melanoma patients. We hypothesize that differences within the host response, specifically the immune cell profile of the SLN, may predict the heterogeneous behavior of stage III melanoma. Methods: A retrospective review of clinically node negative patients undergoing a SLN biopsy at our institution was undertaken. Thirty four SLN positive cases in which the patients also underwent a complete lymph node dissection were identified and the archived FFPE SLN blocks were obtained. A single tumor positive SLN was selected and immunohistochemistry was performed for dendritic cell markers (CD123, CD86, CD11c and HLA-DR), cytotoxic T cells (CD8), anergic T cells (PD-1) and regulatory T cells (Foxp3). Slides were digitized and analyzed for percent of the SLN staining positive for each respective marker using IHCscore. These findings were correlated with risk of further non-SLN disease in the same nodal basin as well as effect on disease-free and overall survival. Results: The SLN exhibited expression of both immune activation (CD8, CD86, and CD11c) and immune suppressive (CD123, PD-1 and Foxp3) markers. HLA-DR expression was significantly higher in females (52.07% vs. 42.32%, p=0.02). No other immune marker was associated with any baseline demographic or clinical variable. Median disease-free survival and overall survival was 6 months and not yet reached and 16 months and not yet reached for patients with and without non-SLN involvement, respectively; however, no difference was noted in any of the SLN immune markers between patients with and without non-SLN involvement. Increased CD8 expression in the SLN was associated with an improvement in disease-free survival (HR 0.94 p = 0.048) but not overall survival (HR 0.93 p = 0.07). In two variable multivariate analyses, CD8 expression remained independent for disease-free survival when adjusted for Breslow depth but not non-SLN involvement. The median disease-free survival for patients with low CD8 expression within the SLN was 19.5 months and median disease-free survival has not been reached in those with high CD8 expression in the SLN after a median of 59 months follow up (log-rank p = 0.05). Conclusion: Previous reports suggest T cell infiltration of melanoma tumors is an important prognostic factor. In this study we found that CD8 T cell accumulation within the SLN was associated with a disease-free survival advantage. Cytotoxic T cell accumulation within the SLN declines early in melanoma and the degree of CD8 depletion corresponds to the risk of disease recurrence. These findings support a key role for effector T cells in the control of melanoma progression. Citation Format: Travis E. Grotz, Aaron S. Mansfield, James W. Jakub, Svetomir N. Markovic, Tina J. Hieken. Immune cell profile of the SLN has prognostic value in stage III melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1266. doi:10.1158/1538-7445.AM2013-1266