Correlation of prevalence of CD68+ macrophages within tumor-draining lymph node basins and overall survival in stage III melanoma patients.

Abstract

e21034 Background: Although it is well-established that melanomas can elicit immune responses, they more often produce factors that adversely impact or block antitumor immunity. Suppressive immune cells such as Foxp3+ regulatory T cells (Treg) and tumor-infiltrating macrophages have been implicated as poor prognostic indicators in other cancer etiologies, but their prognostic value in melanoma has remained unclear. Methods: We performed an immunohistochemical (IHC) analysis of 62 melanoma tumors comprising a spectra of disease stages to assess tumor infiltration by T cells (CD3+, CD4+, CD8+ and Foxp3+ subsets), B cells (CD19+), and macrophages (CD68+). To assess the potential negative impact of tumors on regional immunity, we also analyzed a set of uninvolved regional lymph nodes (LN) harvested from sentinel node positive basins of 28 stage III melanoma patients. All immune markers were correlated with overall survival by univariate Cox regression analyses. Results: Overall, relatively few Foxp3+ T cells or B cells infiltrated melanoma tumors. In contrast, CD68+ macrophages were found to be abundant at all disease stages, typically comprising 5% to 20% of all cells within the tumor parenchyma. Although no significant associations were found with any immune markers in melanoma tumors, Cox regression analysis demonstrated a significant adverse association between the percentage of CD68+ macrophages in uninvolved regional LNs and overall survival (HR=1.93 per 5% increase in CD68+ cells, 95% CI (1.17, 3.18), p=0.01). Kaplan-Meier analyses revealed that stage III patients harboring >15% CD68+ cells in uninvolved regional LNs had a median survival of 2.6 yr vs. 7.7 yr for patients with <15% CD68+ cells. Conclusions: These results suggest that melanoma involvement of regional LNs can adversely impact the immune microenvironment of adjacent uninvolved regional LNs, possibly by facilitating regional immune suppression mediated by CD68+ cells. Pharmacological targeting of tumor-associated CD68+ macrophages may favorably impact survival outcomes for patients with stage III melanoma. No significant financial relationships to disclose.