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

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.

Tumor-infiltrating lymphocytes and tumor-associated macrophages as potential predictors of lymph node metastases in major salivary gland cancers

“…Considering the role of TIL, intratumoral and marginal CD8+, intratumoral FOXP3+, and marginal CD3+ showed to be predictive of LNM. Hiss et al found significant evidence of the increased occurrence of LNM in high-grade acinic cell carcinomas, which also have a greater CD3+ expression with respect to low-grade tumors ( 30 ). In line with our findings, Kesar et al described that tumors with a high total CD8+ showed aggressive behavior in terms of nodal involvement ( 32 ).…”

Targeted Therapy, Chemotherapy, Immunotherapy and Novel Treatment Options for Different Subtypes of Salivary Gland Cancer

“…Moreover, PD-L1 CPS was associated with a poor prognosis regarding metastasis-free survival. The authors concluded that increased immune cell infiltration of T and B cells as well as higher levels of PD-L1 expression in AcCC in association with high-grade transformation, lymph node metastasis, and an unfavorable prognosis suggests a relevant interaction between tumor cells and immune cell infiltrates in a subset of AcCCs, and might represent a rationale for immune checkpoint inhibition [94]. Finally, a study analyzing all histological subtypes including MECs and adenocarcinomas described significantly elevated CD3+, tumor proportion scores (TPS), combined positive scores (CPS), and immune cell scores (IC) in adenocarcinoma NOS compared to ACCs, MECs and AcCCs.…”

An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFβ blockade therapy

“…Recent studies suggest that the spatial context of tumor infiltrating lymphocytes is an important prognostic determinant of tumor progression and response 1 , 2 , 3 . The distribution pattern of tumor infiltrating lymphocytes in the tumor microenvironment (TME) can be classified as three T cell infiltration phenotypes: immune-inflamed, immune-excluded and immune-desert, based on the spatial localization of immune cells with respect to the tumor and stromal compartments 4 .…”