Loss of CD169⁺ Subcapsular Macrophages during Metastatic Spread of Head and Neck Squamous Cell Carcinoma

Abstract

Objective The purpose of this study is to assess CD169 expression in metastatic and nearby tumor-free lymph nodes of patients with head and neck squamous cell carcinoma (SCC). Study Design Retrospective analysis based on immunohistochemistry. Setting Tertiary care center. Subjects and Methods The abundance of CD169+ cells in the subcapsular sinuses (SCSs) of lymph nodes was assessed immunohistochemically in paraffin-embedded tissue samples derived from 22 patients with oral cavity and oropharyngeal SCC. Results SCSs of lymph nodes harboring metastatic SCC contained significantly fewer CD169+ macrophages (106.5 ± 113.6 cells/mm2) compared to nearby tumor-free lymph nodes (321.3 ± 173.4 cells/mm2, P < .001). This observation extended to 21 of the 22 cases investigated. In addition, 6 patients who later developed recurrent disease contained lower numbers of CD169+ cells (268.6 ± 169.5 cells/mm2) in nearby tumor-free lymph nodes compared to 341.0 ± 176.1 cells/mm2 in those who remained disease free ( P = .399). Human papillomavirus (HPV)–positive patients (n = 4) had a 6-fold lower number of CD169+ cells in metastatic nodes (61.2 ± 85.5 cells/mm2) compared to nearby tumor-free lymph nodes (369.5 ± 175.5 cells/mm2, P = .028). In comparison, HPV-negative patients had only a 3-fold reduction (116.6 ± 118.5 cells/mm2 vs 310.6 ± 176.2 cells/mm2, P < .001). Conclusion Metastatic spread of SCC to regional lymph nodes is associated with lower abundance of CD169+ macrophages in the SCSs of draining lymph nodes. These results set the stage for an in-depth investigation into the mechanism(s) by which metastatic SCC controls CD169+ macrophage abundance and its significance as it relates to prognosis and treatment response.

Integrated Analysis Reveals ENDOU as a Biomarker in Head and Neck Squamous Cell Carcinoma Progression

“…In this study, we found ENDOU negative correlates with tumor infiltrating neutrophils, dendritic cells and macrophages, especially M2 macrophages. Macrophages were reported to be involved in HNSCC metastasis (60)(61)(62), chemotherapy (63) and prognosis (64). Macrophages were polarized into M1 and M2 subtypes depending on their environment (65), and were reported to be functionally distinct in cancer (66).…”

Predictive Biomarkers of Severe Immune-Related Adverse Events With Immune Checkpoint Inhibitors: Prevention, Underlying Causes, Intensity, and Consequences

“…PA can increase the cytotoxic activity of T cells and macrophages, thus lowering the risk of metastasis ( 69 ). These modifications are also observed in patients who respond better to ICIs ( 71 – 73 ). Hence, it seems feasible that PA could act as a potential coadjuvant to immunotherapy, as already observed in pre-clinical models ( 74 ).…”

Functions of CD169 positive macrophages in human diseases (Review)

“…In a study of human head and neck squamous cell carcinoma, it was found that RLN metastasis was related to the density of CD169 + macrophages in the subcapsular sinus of the draining lymph nodes. The number of CD169 + macrophages in patients with lymphatic metastasis is lower than that in patients with lymphatic non-metastasis (101). These results suggest that the density of CD169 + macrophages may be used as a potential indicator for evaluating and detecting the clinical prognosis of malignant tumours.…”