Importance: The spread of metastatic squamous cell carcinoma (SCC) to regional lymph nodes in head and neck SCC is traditionally thought to be via a linear path of cancer cells being transported by the lymphatics to draining lymph nodes. With regards to antitumor immunity, regional lymph nodes that drain malignant primary tumors are thought to be the first site where the immune system interacts with tumor cells and their products. It has not been clearly defined why some lymph nodes are more susceptible to regional metastatic spread, while others in the same drainage pattern are spared from tumor infiltration. Lymph node macrophages are important mediators in anti-tumor immunity with CD169+ macrophages acting as a sentinel barrier to the influx of soluble mediators (cytokines and exosomes).
Objective: Examine the macrophage phenotype based on CD169 expression in the subcapsular sinus of positive lymph nodes and nearby negative draining lymph nodes (dLN) in patients with oral cavity SCC.
Methods: CD169 staining was performed on formalin fixed paraffin embedded tissue from seven oral cavity SCC patients with nodal disease. CD169 staining of the positive lymph nodes was compared to the same patient’s nearby negative dLN. Quantitative analysis of CD169 staining was performed using Aperio Imagescope by counting number of positive cells per millimeter squared (mm2).
Results: The subcapsular sinus of negative dLN showed an intensely staining, high density of CD169-positive macrophages. Cancer containing lymph nodes had significantly fewer protective CD169-positive macrophages when compared to negative dLN (164.6 vs. 417.3 CD169-positive macrophages/mm2, 252.6 CD169-positive macrophages/mm2, 95% CI 67.4 to 437.9 CD169-positive macrophages/mm2). For all seven patients, the nodes with SCC metastases had fewer CD169-positive macrophages than adjacent negative dLN.
Conclusions and Relevance: Protective CD169-positive macrophages are more prevalent in the subcapsular sinus of negative draining lymph nodes when compared to nearby lymph nodes with SCC metastases. Further research is necessary to understand the mechanism by which CD169-positive macrophages prevent SCC from metastasizing and its clinical significance related to prognosis and response to treatment.