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.