Impact of immune modulation on sentinel lymph node positivity and outcome in melanoma patients.

Abstract

8561 Background: The interplay between melanoma and the immune system is multifactorial. Immune modulation is a key factor in melanoma metastasis, but its impact on patient management and potential prognostic relevance at the time of primary melanoma diagnosis are not well studied. We investigated the relationship between immune modulation and sentinel lymph node (SLN) positivity and correlated it with outcome in melanoma patients. Methods: We examined T regulatory cells (Tregs: Foxp3+), myeloid dendritic cells (myDCs: CD11c+), and mature dendritic cells (maDCs: CD86+) in lymph node (LN) and primary tissues from 84 melanoma patients prospectively accrued and followed up at New York University Medical Center using immunohistochemistry to detect Foxp3, CD11c, and CD86. The immune response in positive SLN biopsies (SLN+) was compared to that in negative SLN biopsies (SLN-) from patients matched for age, sex, primary tumor thickness/ulceration and negative LNs (LN-) from the same nodal basins of SLN+ patients. Immune cells were quantified as the absolute number in a representative HPF. Decreased immune response was defined as increased Tregs, decreased myDCs, or decreased maDCs. Associations between the expression of these immune modulators, clinicopathologic variables, and outcome were evaluated using univariate and multivariate analyses. Results: Anti-tumor immune response was downregulated both in the SLN+ (n=31) compared to the SLN- (n=53) with significant increase in Tregs (p=0.0002) and decrease in myDCs (p=0.00002) and in the 31 SLN+ compared to the LN- from the same basin with significant increase in Tregs (p=0.0005). Logistic regression models revealed that myDCs and maDCs in the primary tissue were associated with SLN status (p=0.001, 0.01, respectively). Adding Treg expression in the SLN as a predictor variable for recurrence improved the odds ratio in the logistic regression model for stage III from 5.99 to 10.42. Conclusions: Immune response is progressively downregulated with increased tumor involvement of the LNs. Our data support immunosuppression in the SLN as a predictor of worse outcome and suggest that evaluation of local immune profiles can guide the selection of therapy in the adjuvant setting.