Siglec expression in sentinel lymph nodes in patients with oral squamous cell carcinoma

PURPOSE: Siglecs (sialic acid-binding immunoglobulin-like lectins) are immune receptors that modulate leukocyte signaling and influence tumor immunosurveillance. Tumor cells exploit Siglec-sialic acid interactions via hypersialylation to dampen anti-tumor immunity. Sentinel lymph nodes (SLNs) can be conditioned by tumors to form immunosuppressive environments supporting metastasis. This study analyzes Siglec receptor expression in SLN- associated T cells from OSCC patients and evaluates correlations with tumor stage (T stage) and nodal metastasis (N stage). METHODS: Sentinel lymph nodes (SLNs) were collected from OSCC patients undergoing SLN mapping/biopsy as part of standard care. Healthy lymph nodes (HLNs) were collected from non-cancer controls undergoing surgery for benign conditions. Immune cells were isolated and Siglec expression on CD4⁺ and CD8⁺ T cells were quantified using flow cytometry. Within the OSCC cohort, SLNs were classified as metastasis-negative (M⁻) or metastasis-positive (M⁺) based on histopathological assessment. Expression levels were compared between lymph node types and correlated with clinical staging parameters. RESULTS: Distinct patterns of Siglec expression were observed between CD4 + and CD8 + T-cell subsets. Siglec-3 expression on SLN T cells was decreased in metastasis-positive (M⁺) SLNs compared with metastasis-negative (M⁻) SLNs.s. Similarly, Siglec-5 expression on T cells was decreased in SLNs from patients with higher primary tumor stage (T stage) and more extensive nodal metastasis (N stage). CONCLUSION: SLN immune cells exhibit distinctive Siglec expression changes associated with tumor progression. Downregulation of Siglec-3 and Siglec-5 on T cells in metastatic or advanced-stage disease, suggests that Siglec-mediated immune regulation contributes to the immunosuppressive pre-metastatic niche. These findings provide first-time evidence of altered Siglec pathways in SLNs, highlighting their potential utility as immune biomarkers and therapeutic targets in solid malignancies.