Abstract
Salivary gland carcinomas (SGC) are rare and heterogeneous tumors with limited therapeutic options in advanced stages. Recent evidence suggests a potential role of the tumor immune microenvironment (TME) in disease progression. This study aimed to investigate the immune profile of SGCs by analyzing tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 expression, and to assess their correlation with histological grade and clinical outcome. A retrospective analysis was conducted on 103 SGC cases. Immunohistochemistry for CD3, CD4, CD8, CD20, CD56, PD-1, PD-L1, FOXP3, CD68, and CD163 was performed. Digital slide analysis was carried out in intratumoral and peritumoral regions using QuPath software. High intratumoral FOXP3 + Tregs were significantly associated with high-grade tumors and worse progression-free survival (PFS) (p = 0.009). A higher peritumoral CD3 + T cell density correlated with poor prognosis (p = 0.046). Concordance between pathologist assessments and QuPath quantification was moderate to high (Cohen’s K = 0.71). In conclusion, intratumoral Tregs and peritumoural T lymphocytes may be used as negative prognostic biomarkers. Future multicentric studies and AI (Artificial Intelligence)-driven analyses could enhance immune characterization and guide immunotherapeutic strategies in SGC.
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All the information regarding the patients is available in the database of Pathology and Surgery Unit of Azienda Toscana Nord-Ovest on direct request to the corresponding author (address [francesco.vasuri2@unibo.it](mailto: francesco.vasuri2@unibo.it) ).
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DA Conceptualization, Data curation, Writing – original draft; FV Writing – original draft; LN Data curation, Formal analysis; LS Supervision; LM Formal analysis Investigation, Methodology; CS Formal analysis, Investigation; EC Data curation, Methodology; LM Investigation; GB Investigation; EN Methodology; AA Conceptualization, Supervision, Validation; AF Supervision; MRA Conceptualization, Writing – review and editing.
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This study was conducted according to the guidelines of the Declaration of Helsinki and the STROBE guidelines, and approved by the Ethics Committee of Azienda Sanitaria Toscana Nord-Ovest (code 19542). Informed Consent was obtained at the moment of surgery.
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Anconelli, D., Vasuri, F., Novelli, L. et al. A high density of T-cell lymphocytes and Tregs subset correlate to a worse survival in major salivary gland carcinomas. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39357-y
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DOI: https://doi.org/10.1038/s41598-026-39357-y
