Cargando…

EPEN-20. PDL1 expression and tumor-infiltrating immune cell subpopulations: The role of immune-checkpoint molecules in the prognosis of patients with supratentorial ependymoma and its correlation to survival

Immune checkpoint blockade of the programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has shifted the way advanced cancers are treated. The 'ST-RELA fusion positive' and 'PF-A' molecular subgroups of ependymomas (EPN) have a dismal prognosis. AIMS: This study is...

Descripción completa

Detalles Bibliográficos
Autores principales: Malik, Rafat, Sharma, Agrima, Kumar, Amandeep, Singh, Manmohan, Suri, Vaishali, Sharma, Mehar Chand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164749/
http://dx.doi.org/10.1093/neuonc/noac079.157
_version_ 1784720209067638784
author Malik, Rafat
Sharma, Agrima
Kumar, Amandeep
Singh, Manmohan
Suri, Vaishali
Sharma, Mehar Chand
author_facet Malik, Rafat
Sharma, Agrima
Kumar, Amandeep
Singh, Manmohan
Suri, Vaishali
Sharma, Mehar Chand
author_sort Malik, Rafat
collection PubMed
description Immune checkpoint blockade of the programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has shifted the way advanced cancers are treated. The 'ST-RELA fusion positive' and 'PF-A' molecular subgroups of ependymomas (EPN) have a dismal prognosis. AIMS: This study is undertaken to look for immunological microenvironment in ependymomas. Based on L1CAM protein expression and/or the presence of RELA/YAP1 fusion transcripts by RT-PCR, all supratentorial (ST) Grade-II/III EPNs were classified as ST-RELA, ST-YAP, and ST-not otherwise specified (NOS). Based on H3K27me3 protein expression and chromosome 1q gain, all posterior fossa (PF) EPNs were classified as PF-A or PF-B. PD-L1 (SP263, Ventana) and CD8 immunohistochemistry was performed. The enrichment of RelA protein at the PDL1 promoter site was investigated using chromatin immunoprecipitation-qPCR (ChIP-qPCR) in three ST-RELA samples. A total of 83 intracranial EPNs were included in our preliminary data, and we discovered that PD-L1 expression correlates with increasing cytotoxic T-lymphocyte infiltrates in intracranial ependymomas using PD-L1 and CD8 IHC. The majority of PD-L1-positive intracranial EPNs are members of the ST-RELA subset, which also has the highest CTL density. Our findings suggest that ST-RELA EPNs could be used in immunotherapy to target immune checkpoint modulators. To further this research, we are looking into the presence of tumour infiltrating cells such as CD3, CD8, CD163, FOXP3, and others, which can aid in characterising the tumour microenvironment in cell types expressing PD-L1.This study will also be used to predict the prognostic significance of PD-L1/PD1 and other tumour cell infiltrating biomarkers in ependymomas and correlate it with survival outcomes.
format Online
Article
Text
id pubmed-9164749
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-91647492022-06-05 EPEN-20. PDL1 expression and tumor-infiltrating immune cell subpopulations: The role of immune-checkpoint molecules in the prognosis of patients with supratentorial ependymoma and its correlation to survival Malik, Rafat Sharma, Agrima Kumar, Amandeep Singh, Manmohan Suri, Vaishali Sharma, Mehar Chand Neuro Oncol Ependymoma Immune checkpoint blockade of the programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has shifted the way advanced cancers are treated. The 'ST-RELA fusion positive' and 'PF-A' molecular subgroups of ependymomas (EPN) have a dismal prognosis. AIMS: This study is undertaken to look for immunological microenvironment in ependymomas. Based on L1CAM protein expression and/or the presence of RELA/YAP1 fusion transcripts by RT-PCR, all supratentorial (ST) Grade-II/III EPNs were classified as ST-RELA, ST-YAP, and ST-not otherwise specified (NOS). Based on H3K27me3 protein expression and chromosome 1q gain, all posterior fossa (PF) EPNs were classified as PF-A or PF-B. PD-L1 (SP263, Ventana) and CD8 immunohistochemistry was performed. The enrichment of RelA protein at the PDL1 promoter site was investigated using chromatin immunoprecipitation-qPCR (ChIP-qPCR) in three ST-RELA samples. A total of 83 intracranial EPNs were included in our preliminary data, and we discovered that PD-L1 expression correlates with increasing cytotoxic T-lymphocyte infiltrates in intracranial ependymomas using PD-L1 and CD8 IHC. The majority of PD-L1-positive intracranial EPNs are members of the ST-RELA subset, which also has the highest CTL density. Our findings suggest that ST-RELA EPNs could be used in immunotherapy to target immune checkpoint modulators. To further this research, we are looking into the presence of tumour infiltrating cells such as CD3, CD8, CD163, FOXP3, and others, which can aid in characterising the tumour microenvironment in cell types expressing PD-L1.This study will also be used to predict the prognostic significance of PD-L1/PD1 and other tumour cell infiltrating biomarkers in ependymomas and correlate it with survival outcomes. Oxford University Press 2022-06-03 /pmc/articles/PMC9164749/ http://dx.doi.org/10.1093/neuonc/noac079.157 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Ependymoma
Malik, Rafat
Sharma, Agrima
Kumar, Amandeep
Singh, Manmohan
Suri, Vaishali
Sharma, Mehar Chand
EPEN-20. PDL1 expression and tumor-infiltrating immune cell subpopulations: The role of immune-checkpoint molecules in the prognosis of patients with supratentorial ependymoma and its correlation to survival
title EPEN-20. PDL1 expression and tumor-infiltrating immune cell subpopulations: The role of immune-checkpoint molecules in the prognosis of patients with supratentorial ependymoma and its correlation to survival
title_full EPEN-20. PDL1 expression and tumor-infiltrating immune cell subpopulations: The role of immune-checkpoint molecules in the prognosis of patients with supratentorial ependymoma and its correlation to survival
title_fullStr EPEN-20. PDL1 expression and tumor-infiltrating immune cell subpopulations: The role of immune-checkpoint molecules in the prognosis of patients with supratentorial ependymoma and its correlation to survival
title_full_unstemmed EPEN-20. PDL1 expression and tumor-infiltrating immune cell subpopulations: The role of immune-checkpoint molecules in the prognosis of patients with supratentorial ependymoma and its correlation to survival
title_short EPEN-20. PDL1 expression and tumor-infiltrating immune cell subpopulations: The role of immune-checkpoint molecules in the prognosis of patients with supratentorial ependymoma and its correlation to survival
title_sort epen-20. pdl1 expression and tumor-infiltrating immune cell subpopulations: the role of immune-checkpoint molecules in the prognosis of patients with supratentorial ependymoma and its correlation to survival
topic Ependymoma
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164749/
http://dx.doi.org/10.1093/neuonc/noac079.157
work_keys_str_mv AT malikrafat epen20pdl1expressionandtumorinfiltratingimmunecellsubpopulationstheroleofimmunecheckpointmoleculesintheprognosisofpatientswithsupratentorialependymomaanditscorrelationtosurvival
AT sharmaagrima epen20pdl1expressionandtumorinfiltratingimmunecellsubpopulationstheroleofimmunecheckpointmoleculesintheprognosisofpatientswithsupratentorialependymomaanditscorrelationtosurvival
AT kumaramandeep epen20pdl1expressionandtumorinfiltratingimmunecellsubpopulationstheroleofimmunecheckpointmoleculesintheprognosisofpatientswithsupratentorialependymomaanditscorrelationtosurvival
AT singhmanmohan epen20pdl1expressionandtumorinfiltratingimmunecellsubpopulationstheroleofimmunecheckpointmoleculesintheprognosisofpatientswithsupratentorialependymomaanditscorrelationtosurvival
AT surivaishali epen20pdl1expressionandtumorinfiltratingimmunecellsubpopulationstheroleofimmunecheckpointmoleculesintheprognosisofpatientswithsupratentorialependymomaanditscorrelationtosurvival
AT sharmameharchand epen20pdl1expressionandtumorinfiltratingimmunecellsubpopulationstheroleofimmunecheckpointmoleculesintheprognosisofpatientswithsupratentorialependymomaanditscorrelationtosurvival