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Prognostic Significance of CD169+ Lymph Node Sinus Macrophages in Patients with Malignant Melanoma
Yoichi Saito1, Koji Ohnishi1, Azusa Miyashita2
1Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Abstract:
CD169 (sialoadhesin) is a sialic acid receptor that is specifically expressed on macrophages, including lymph node sinus macrophages. Animal studies suggest that CD169(+) macrophages in lymph nodes have properties in preventing cancers. In order to determine the significance of CD169(+) macrophages in patients with malignant melanoma, we evaluated tissue samples from 93 patients to investigate CD169 expression in regional lymph nodes (RLN) and determine the relationship of this expression with overall survival and various clinicopathologic factors. Higher densities of CD169(+) cells were significantly associated with longer overall survival (P = 0.001). A multivariate analysis showed that the density of CD169(+) cells was an independent prognostic factor, with higher densities correlating with higher density of CD8(+) cytotoxic T cells within tumor sites. High CD169 expression in macrophages could be stimulated by IFNα in vitro, and in RLNs, IFNα-producing macrophages and CD303(+) plasmacytoid dendritic cells were identified surrounding CD169(+) macrophages. These data suggest that IFNα-stimulated CD169(+) macrophages in RLNs are closely involved in T-cell-mediated antitumor immunity and may be a useful marker for assessing the clinical prognosis and monitoring antitumor immunity in patients with malignant melanoma.
Insights
Higher densities of CD169 (sialoadhesin) expressing macrophages in lymph nodes correlate with improved survival for malignant melanoma patients. These CD169(+) macrophages are linked to T-cell immunity and may serve as a prognostic marker.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- CD169 (sialoadhesin) is a sialic acid receptor expressed on macrophages.
- Animal studies suggest CD169(+) macrophages in lymph nodes possess anti-cancer properties.
- The role of CD169(+) macrophages in human malignant melanoma prognosis is not well understood.
Purpose of the Study:
- To investigate CD169 expression in regional lymph nodes (RLN) of malignant melanoma patients.
- To determine the association between CD169 expression density and patient survival.
- To explore the relationship between CD169(+) macrophages and antitumor immunity.
Main Methods:
- Analysis of tissue samples from 93 malignant melanoma patients.
- Quantification of CD169(+) cell density in regional lymph nodes.
- Multivariate analysis to assess prognostic significance and correlation with CD8(+) T cells.
- In vitro stimulation of CD169 expression with IFNα.
Main Results:
- Higher densities of CD169(+) cells in RLNs were significantly associated with longer overall survival (P = 0.001).
- CD169(+) cell density was an independent prognostic factor.
- Increased CD169(+) density correlated with higher CD8(+) cytotoxic T cell density.
- IFNα stimulated CD169 expression in vitro; IFNα-producing macrophages and CD303(+) dendritic cells were found near CD169(+) macrophages in RLNs.
Conclusions:
- IFNα-stimulated CD169(+) macrophages in RLNs are involved in T-cell-mediated antitumor immunity.
- CD169(+) macrophage density is a significant independent prognostic factor in malignant melanoma.
- CD169 expression may serve as a valuable marker for prognosis and monitoring antitumor immunity in melanoma patients.
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