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

Objectives: The aim of this study was to assess the number of tumour-infiltrating lymphocytes (TILs) and the expression of <i>Programmed Cell Death 1 Ligand 1</i> (PD-L1) in Acinic Cell Carcinoma (AciCC) of the salivary glands, to enable a correlation with clinico-pathological features a...

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Main Authors: Selina Hiss, Markus Eckstein, Patricia Segschneider, Konstantinos Mantsopoulos, Heinrich Iro, Arndt Hartmann, Abbas Agaimy, Florian Haller, Sarina K. Mueller
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/5/965
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record_format Article
collection DOAJ
language English
format Article
sources DOAJ
author Selina Hiss
Markus Eckstein
Patricia Segschneider
Konstantinos Mantsopoulos
Heinrich Iro
Arndt Hartmann
Abbas Agaimy
Florian Haller
Sarina K. Mueller
spellingShingle Selina Hiss
Markus Eckstein
Patricia Segschneider
Konstantinos Mantsopoulos
Heinrich Iro
Arndt Hartmann
Abbas Agaimy
Florian Haller
Sarina K. Mueller
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
Cancers
PD-L1
tumour-infiltrating lymphocytes
checkpoint inhibition
immuno-oncology
acinic cell carcinoma
author_facet Selina Hiss
Markus Eckstein
Patricia Segschneider
Konstantinos Mantsopoulos
Heinrich Iro
Arndt Hartmann
Abbas Agaimy
Florian Haller
Sarina K. Mueller
author_sort Selina Hiss
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher MDPI AG
series Cancers
issn 2072-6694
publishDate 2021-02-01
description Objectives: The aim of this study was to assess the number of tumour-infiltrating lymphocytes (TILs) and the expression of <i>Programmed Cell Death 1 Ligand 1</i> (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 (<i>p</i> = 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.
topic PD-L1
tumour-infiltrating lymphocytes
checkpoint inhibition
immuno-oncology
acinic cell carcinoma
url https://www.mdpi.com/2072-6694/13/5/965
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AT markuseckstein tumourinfiltratinglymphocytestilsandpdl1expressioncorrelatewithlymphnodemetastasishighgradetransformationandshortermetastasisfreesurvivalinpatientswithaciniccellcarcinomaaciccofthesalivaryglands
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AT heinrichiro tumourinfiltratinglymphocytestilsandpdl1expressioncorrelatewithlymphnodemetastasishighgradetransformationandshortermetastasisfreesurvivalinpatientswithaciniccellcarcinomaaciccofthesalivaryglands
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AT sarinakmueller tumourinfiltratinglymphocytestilsandpdl1expressioncorrelatewithlymphnodemetastasishighgradetransformationandshortermetastasisfreesurvivalinpatientswithaciniccellcarcinomaaciccofthesalivaryglands
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spelling doaj-4f051a25e68e4b88869148b58fd556482021-02-26T00:06:09ZengMDPI AGCancers2072-66942021-02-011396596510.3390/cancers13050965Tumour-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 GlandsSelina Hiss0Markus Eckstein1Patricia Segschneider2Konstantinos Mantsopoulos3Heinrich Iro4Arndt Hartmann5Abbas Agaimy6Florian Haller7Sarina K. Mueller8Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054 Erlangen, GermanyInstitute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054 Erlangen, GermanyInstitute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054 Erlangen, GermanyDepartment of Otorhinolaryngology, Head & Neck Surgery, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Waldstrasse 1, 91054 Erlangen, GermanyDepartment of Otorhinolaryngology, Head & Neck Surgery, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Waldstrasse 1, 91054 Erlangen, GermanyInstitute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054 Erlangen, GermanyInstitute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054 Erlangen, GermanyInstitute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054 Erlangen, GermanyDepartment of Otorhinolaryngology, Head & Neck Surgery, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Waldstrasse 1, 91054 Erlangen, GermanyObjectives: The aim of this study was to assess the number of tumour-infiltrating lymphocytes (TILs) and the expression of <i>Programmed Cell Death 1 Ligand 1</i> (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 (<i>p</i> = 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.https://www.mdpi.com/2072-6694/13/5/965PD-L1tumour-infiltrating lymphocytescheckpoint inhibitionimmuno-oncologyacinic cell carcinoma