Immune cell profile of sentinel lymph nodes in patients with malignant melanoma – FOXP3+ cell density in cases with positive sentinel node status is associated with unfavorable clinical outcome

Journal of Translational Medicine

Andrea Ladányi²  István Gaudi¹  Szabolcs Horváth²  Vanda Plótár²  Gabriella Liszkay³  Tímea Sebestyén⁵  Anita Mohos⁴ 

[1] National Cancer Registry, National Institute of Oncology, Budapest, Hungary;Department of Surgical and Molecular Pathology, National Institute of Oncology, 7-9. Ráth György u., Budapest, H-1122, Hungary;Department of Dermatology, National Institute of Oncology, Budapest, Hungary;1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary;Department of Pathology, St. John’s Hospital, Budapest, Hungary

关键词: Immunohistochemistry;    Dendritic cell;    Regulatory T cell;    Activated T cell;    Sentinel lymph node;    Melanoma;   

Others  :  828043
DOI  :  10.1186/1479-5876-11-43

 received in 2012-10-17, accepted in 2013-02-05,  发布年份 2013

【 摘 要 】

Background

Besides being a preferential site of early metastasis, the sentinel lymph node (SLN) is also a privileged site of T-cell priming, and may thus be an appropriate target for investigating cell types involved in antitumor immune reactions.

Methods

In this retrospective study we determined the prevalence of OX40⁺ activated T lymphocytes, FOXP3⁺ (forkhead box P3) regulatory T cells, DC-LAMP⁺ (dendritic cell-lysosomal associated membrane protein) mature dendritic cells (DCs) and CD123⁺ plasmacytoid DCs by immunohistochemistry in 100 SLNs from 60 melanoma patients. Density values of each cell type in SLNs were compared to those in non-sentinel nodes obtained from block dissections (n = 37), and analyzed with regard to associations with clinicopathological parameters and disease outcome.

Results

Sentinel nodes showed elevated amount of all cell types studied in comparison to non-sentinel nodes. Metastatic SLNs had higher density of OX40⁺ lymphocytes compared to tumor-negative nodes, while no significant difference was observed in the case of the other cell types studied. In patients with positive sentinel node status, high amount of FOXP3⁺ cells in SLNs was associated with shorter progression-free (P = 0.0011) and overall survival (P = 0.0014), while no significant correlation was found in the case of sentinel-negative patients. The density of OX40⁺, CD123⁺ or DC-LAMP⁺ cells did not show significant association with the outcome of the disease.

Conclusions

Taken together, our results are compatible with the hypothesis of functional competence of sentinel lymph nodes based on the prevalence of the studied immune cells. The density of FOXP3⁺ lymphocytes showed association with progression and survival in patients with positive SLN status, while the other immune markers studied did not prove of prognostic importance. These results, together with our previous findings on the prognostic value of activated T cells and mature DCs infiltrating primary melanomas, suggest that immune activation-associated markers in the primary tumor may have a higher impact than those in SLNs on the prognosis of the patients. On the other hand, FOXP3⁺ cell density in SLNs, but not in the primary tumor, was found predictive of disease outcome in melanoma patients.

【 授权许可】

   
2013 Mohos et al; licensee BioMed Central Ltd.

【 图 表 】

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Figure 3.

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