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Updated: Jun 4, 2026
Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma
Published on: September 8, 2021
Molecular analysis of melanoma-induced sentinel lymph node immune dysfunction
Jonathan H Lee1, Yun Chen, Joseph L Chan
1Department of Surgery/Division of Surgical Oncology, CINJ/UMDNJ/RWJ Medical School, The Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA. leejh1@umdnj.edu
Melanoma tumor burden in sentinel lymph nodes (SLNs) correlates with immune dysfunction, indicated by increased indoleamine-2,3-dioxygenase (IDO) and Foxp3 expressions. Interferon-gamma (IFNγ) plays a key role in these tumor-induced immunological changes.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Sentinel lymph nodes (SLNs) in melanoma patients often exhibit tumor-induced immune dysfunction.
- Previous research identified co-regulation of indoleamine-2,3-dioxygenase (IDO)-expressing immunosuppressive dendritic cells (DCs) by IL-10 and IFNγ in melanoma SLNs.
Purpose of the Study:
- To investigate the relationship between melanoma SLN tumor burden and the extent of SLN immune dysfunction.
- To utilize SLN immune dysfunction as a model for studying tumor-induced immune dysfunction.
Main Methods:
- Quantitative real-time PCR was used to measure gene expression of cytokines (IL-4, IL-10, IFNγ, TGFβ, GM-CSF) and immune cell surrogates (IDO-expressing DCs, Foxp3-expressing T-regs).
- Gene expression levels were correlated with SLN tumor burden (MART1) and with each other.
- Statistical analyses included Student's t-test and stepwise multivariate regression, with significance set at P < 0.05.
Main Results:
- Of 74 patients, 10 (13.5%) had tumor-positive SLNs, with significant MART1 gene expression difference between tumor-positive and negative SLNs (P=0.04).
- IFNγ gene expression independently correlated with MART1 gene expression (P < 0.0001, r=0.91).
- IFNγ, IL-10, and TGFβ gene expressions correlated with IDO; IFNγ and GM-CSF correlated with Foxp3; MART1 correlated with IDO and Foxp3.
Conclusions:
- SLN tumor burden is associated with increased immunosuppressive IDO and Foxp3 expressions in melanoma patients' SLNs.
- Melanoma appears to induce specific cytokine expressions that promote immune suppression within the SLN.
- IFNγ is identified as the sole cytokine correlating with SLN tumor burden, suggesting a central role in tumor-driven immune alterations within the SLN microenvironment.
