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.

Selina Hiss,Heinrich Iro,Abbas Agaimy,Patricia Segschneider,Markus Eckstein,Sarina K Mueller,Florian Haller,Konstantinos Mantsopoulos,Arndt Hartmann

doi:10.3390/cancers13050965

Selina Hiss, Heinrich Iro + Show 7 more

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https://doi.org/10.3390/cancers13050965

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Abstract

Simple SummaryAcinic 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.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.

Highlights

Acinic cell carcinoma (AciCC) constitutes the third most common malignant epithelial neoplasm of the salivary glands [1]
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
Clinico-pathological data including follow-up were collected from the clinical archive, with (i) recurrence-free survival defined as time period from date of surgery until the date of local recurrence, (ii) metastasis-free-survival defined as time period from date of surgery until the date of distant metastasis and (iii) disease-specific survival defined as time period from date of surgery until the date of death from tumour disease

Summary

Introduction

Acinic cell carcinoma (AciCC) constitutes the third most common malignant epithelial neoplasm of the salivary glands [1]. Compared to other salivary gland malignancies, patients with AciCC generally have a favourable prognosis with a 10-year relative survival of 88% [1,2]. Clinically occult regional lymph node metastases have been reported in up to 22% of patients with AciCC, and elective neck dissection for each patient with AciCC independent of other clinico-pathological parameters has been suggested by a recent study [5,12,13,14] High-grade transformation in AciCC has originally been defined as the presence of a dedifferentiated component with features of high-grade adenocarcinoma or poorly differentiated carcinoma next to a differentiated conventional low-grade AciCC component, cases fulfilling this definition are exceedingly rare [15,16,17]. Several histomorphological features including increased mitotic counts, nuclear pleomorphism, necrosis and infiltrative growth pattern correlate with reduced survival in patients with AciCC [3,5,18,19] but no uniform histological grading system for AciCC has been established yet [4,5]

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