The PD-L1/PD-1 axis expression on tumor-infiltrating immune cells and tumor cells in pediatric rhabdomyosarcoma.


Journal

Pathology, research and practice
ISSN: 1618-0631
Titre abrégé: Pathol Res Pract
Pays: Germany
ID NLM: 7806109

Informations de publication

Date de publication:
Dec 2019
Historique:
received: 05 07 2019
revised: 15 10 2019
accepted: 17 10 2019
pubmed: 11 11 2019
medline: 28 4 2020
entrez: 10 11 2019
Statut: ppublish

Résumé

Activation of immune checkpoints, e.g. PD-1/PD-L1 axis, in cancer microenvironment, enables evasion of host anti-cancer immune response and drives tumor progression. To date, there have been only a few studies analyzing PD-1/PD-L1 expression in pediatric malignancies. In the current study, we aimed to assess PD-L1 and PD-1 expression in pediatric rhabdomyosarcoma (RMS) and to investigate their clinicopathological associations. The study enrolled 31 children with RMS. Tissue microarrays with representative tumor tissue samples were stained with anti-PD-1 NAT105 clone (Ventana, Roche) and two different antibodies against PD-L1: SP142 (Ventana, Roche) and 22C3 (DAKO). Adequate positive controls were applied. Their expression was assessed in tumor-associated immune cells (TAICs) and in the tumor cells separately. We did not detect any positive PD-L1 staining in analyzed tumors using SP142 antibody; however, in 11 cases (35.48%) its expression was revealed by means of 22C3 clone. The staining was restricted to TAICs in all cases, which no reaction in tumor cells. The 5-year relapse free survival (RFS) rate was significantly higher in PD-L1 positive cases (61.5% vs 25.0%, p = 0.024), but it most likely results from more frequent PD-L1 expression in low-stage RMS. PD-1 expression on TAICs was detected in 7 cases and did not influence the prognosis. We found that PD-L1 expression on TAICs, as detected with the use of 22C3 clone but not SP142 antibody, tends to be associated with low-stage RMS in children. PD-1 expression on TAICs in RMS is neither associated with distinct clinical course nor with clinicopathological features.

Sections du résumé

BACKGROUND BACKGROUND
Activation of immune checkpoints, e.g. PD-1/PD-L1 axis, in cancer microenvironment, enables evasion of host anti-cancer immune response and drives tumor progression. To date, there have been only a few studies analyzing PD-1/PD-L1 expression in pediatric malignancies.
AIM OBJECTIVE
In the current study, we aimed to assess PD-L1 and PD-1 expression in pediatric rhabdomyosarcoma (RMS) and to investigate their clinicopathological associations.
MATERIALS AND METHODS METHODS
The study enrolled 31 children with RMS. Tissue microarrays with representative tumor tissue samples were stained with anti-PD-1 NAT105 clone (Ventana, Roche) and two different antibodies against PD-L1: SP142 (Ventana, Roche) and 22C3 (DAKO). Adequate positive controls were applied. Their expression was assessed in tumor-associated immune cells (TAICs) and in the tumor cells separately.
RESULTS RESULTS
We did not detect any positive PD-L1 staining in analyzed tumors using SP142 antibody; however, in 11 cases (35.48%) its expression was revealed by means of 22C3 clone. The staining was restricted to TAICs in all cases, which no reaction in tumor cells. The 5-year relapse free survival (RFS) rate was significantly higher in PD-L1 positive cases (61.5% vs 25.0%, p = 0.024), but it most likely results from more frequent PD-L1 expression in low-stage RMS. PD-1 expression on TAICs was detected in 7 cases and did not influence the prognosis.
CONCLUSIONS CONCLUSIONS
We found that PD-L1 expression on TAICs, as detected with the use of 22C3 clone but not SP142 antibody, tends to be associated with low-stage RMS in children. PD-1 expression on TAICs in RMS is neither associated with distinct clinical course nor with clinicopathological features.

Identifiants

pubmed: 31704149
pii: S0344-0338(19)31354-8
doi: 10.1016/j.prp.2019.152700
pii:
doi:

Substances chimiques

B7-H1 Antigen 0
Biomarkers, Tumor 0
CD274 protein, human 0
PDCD1 protein, human 0
Programmed Cell Death 1 Receptor 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

152700

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.

Auteurs

Anna Gabrych (A)

Department of Pediatrics, Hematology and Oncology, Medical University of Gdańsk, Gdańsk, Poland.

Rafał Pęksa (R)

Department of Pathology, Medical University of Gdańsk, Gdańsk, Poland.

Michał Kunc (M)

Department of Pathology, Medical University of Gdańsk, Gdańsk, Poland.

Małgorzata Krawczyk (M)

Department of Pediatrics, Hematology and Oncology, Medical University of Gdańsk, Gdańsk, Poland.

Ewa Izycka-Swieszewska (E)

Department of Pathology and Neuropathology, Medical University of Gdańsk, Gdańsk, Poland.

Wojciech Biernat (W)

Department of Pathology, Medical University of Gdańsk, Gdańsk, Poland.

Ewa Bień (E)

Department of Pediatrics, Hematology and Oncology, Medical University of Gdańsk, Gdańsk, Poland. Electronic address: ebien@gumed.edu.pl.

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Classifications MeSH