Tumour-Infiltrating Lymphocytes (TILs) and PD-L1 Expression Correlate with Lymph Node Metastasis, High-Grade Transformation and Shorter Metastasis-Free Survival in Patients with Acinic Cell Carcinoma (AciCC) of the Salivary Glands

SIMPLE SUMMARY: Acinic cell carcinoma (AciCC) is a malignant neoplasm of the salivary glands. The assessment of tumour-infiltrating lymphocytes (TILs) and the evaluation of the expression of Programmed Cell Death 1 Ligand 1 (PD-L1) can provide prognostic information and may be valuable in predicting response to immuno-oncological treatments. The aim of our retrospective study was to measure the number of TILs and PD-L1 expression in 36 AciCCs and to analyze their prognostic impact based on the correlation with clinico-pathological features. Increased numbers of TILs and a higher expression of PD-L1 were associated with tumour high-grade transformation and the presence of lymph node metastasis. Moreover, higher expression of PD-L1 correlated with a shorter period of metastasis-free survival. As a result, the correlation between TILs, PD-L1 expression, high-grade transformation and lymph node metastasis indicates a relevant interaction between tumour cells and immune cell infiltration and might constitute the basis for innovative immunological therapy attempts. ABSTRACT: Objectives: The aim of this study was to assess the number of tumour-infiltrating lymphocytes (TILs) and the expression of Programmed Cell Death 1 Ligand 1 (PD-L1) in Acinic Cell Carcinoma (AciCC) of the salivary glands, to enable a correlation with clinico-pathological features and to analyse their prognostic impact. Methods: This single centre retrospective study represents a cohort of 36 primary AciCCs with long-term clinical follow-up. Immunohistochemically defined immune cell subtypes, i.e., those expressing T-cell markers (CD3, CD4 and CD8) or a B-cell marker (CD20) were characterized on tumour tissue sections. The number of TILs was quantitatively evaluated using software for digital bioimage analysis (QuPath). PD-L1 expression on the tumour cells and on immune cells was assessed immunohistochemically employing established scoring criteria: tumour proportion score (TPS), Ventana immune cell score (IC-Score) and combined positive score (CPS). Results: Higher numbers of tumour-infiltrating T- and B-lymphocytes were significantly associated with high-grade transformation. Furthermore, higher counts of T-lymphocytes correlated with node-positive disease. There was a significant correlation between higher levels of PD-L1 expression and lymph node metastases as well as the occurrence of high-grade transformation. Moreover, PD-L1 CPS was associated with poor prognosis regarding metastasis-free survival (p = 0.049). Conclusions: The current study is the first to demonstrate an association between PD-L1 expression and lymph node metastases as well as grading in AciCCs. In conclusion, increased immune cell infiltration of T and B cells as well as higher levels of PD-L1 expression in AciCC in association with high-grade transformation, lymph node metastasis and unfavourable prognosis suggests a relevant interaction between tumour cells and immune cell infiltrates in a subset of AciCCs, and might represent a rationale for immune checkpoint inhibition.