A high density of T-cell lymphocytes and Tregs subset correlate to a worse survival in major salivary gland carcinomas

: 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.