Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors.
BACKGROUND:Central nervous system (CNS) primitive neuroectodermal tumors (PNETs) are malignant primary brain tumors that occur in young infants. Using current standard therapy, up to 80% of the children still dies from recurrent disease. Cellular immunotherapy might be key to improve overall surviva...
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doaj-9a2752e8ddf64ec09c3b750ce92c95da2020-11-25T00:03:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01113e015146510.1371/journal.pone.0151465Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors.Jeroen F VermeulenWim van HeckeWim G M SplietJosé Villacorta HidalgoPaul FischRoel BroekhuizenNiels BovenschenBACKGROUND:Central nervous system (CNS) primitive neuroectodermal tumors (PNETs) are malignant primary brain tumors that occur in young infants. Using current standard therapy, up to 80% of the children still dies from recurrent disease. Cellular immunotherapy might be key to improve overall survival. To achieve efficient killing of tumor cells, however, immunotherapy has to overcome cancer-associated strategies to evade the cytotoxic immune response. Whether CNS-PNETs can evade the immune response remains unknown. METHODS:We examined by immunohistochemistry the immune response and immune evasion strategies in pediatric CNS-PNETs. RESULTS:Here, we show that CD4+, CD8+, γδ-T-cells, and Tregs can infiltrate pediatric CNS-PNETs, although the activation status of cytotoxic cells is variable. Pediatric CNS-PNETs evade immune recognition by downregulating cell surface MHC-I and CD1d expression. Intriguingly, expression of SERPINB9, SERPINB1, and SERPINB4 is acquired during tumorigenesis in 29%, 29%, and 57% of the tumors, respectively. CONCLUSION:We show for the first time that brain tumors express direct granzyme inhibitors (serpins) as a potential mechanism to overcome cellular cytotoxicity, which may have consequences for cellular immunotherapy.http://europepmc.org/articles/PMC4786147?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jeroen F Vermeulen Wim van Hecke Wim G M Spliet José Villacorta Hidalgo Paul Fisch Roel Broekhuizen Niels Bovenschen |
spellingShingle |
Jeroen F Vermeulen Wim van Hecke Wim G M Spliet José Villacorta Hidalgo Paul Fisch Roel Broekhuizen Niels Bovenschen Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors. PLoS ONE |
author_facet |
Jeroen F Vermeulen Wim van Hecke Wim G M Spliet José Villacorta Hidalgo Paul Fisch Roel Broekhuizen Niels Bovenschen |
author_sort |
Jeroen F Vermeulen |
title |
Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors. |
title_short |
Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors. |
title_full |
Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors. |
title_fullStr |
Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors. |
title_full_unstemmed |
Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors. |
title_sort |
pediatric primitive neuroectodermal tumors of the central nervous system differentially express granzyme inhibitors. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
BACKGROUND:Central nervous system (CNS) primitive neuroectodermal tumors (PNETs) are malignant primary brain tumors that occur in young infants. Using current standard therapy, up to 80% of the children still dies from recurrent disease. Cellular immunotherapy might be key to improve overall survival. To achieve efficient killing of tumor cells, however, immunotherapy has to overcome cancer-associated strategies to evade the cytotoxic immune response. Whether CNS-PNETs can evade the immune response remains unknown. METHODS:We examined by immunohistochemistry the immune response and immune evasion strategies in pediatric CNS-PNETs. RESULTS:Here, we show that CD4+, CD8+, γδ-T-cells, and Tregs can infiltrate pediatric CNS-PNETs, although the activation status of cytotoxic cells is variable. Pediatric CNS-PNETs evade immune recognition by downregulating cell surface MHC-I and CD1d expression. Intriguingly, expression of SERPINB9, SERPINB1, and SERPINB4 is acquired during tumorigenesis in 29%, 29%, and 57% of the tumors, respectively. CONCLUSION:We show for the first time that brain tumors express direct granzyme inhibitors (serpins) as a potential mechanism to overcome cellular cytotoxicity, which may have consequences for cellular immunotherapy. |
url |
http://europepmc.org/articles/PMC4786147?pdf=render |
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