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IMMU-27. ANALYSIS OF IMMUNE SIGNATURES IN PEDIATRIC GLIOBLASTOMAS FOR PATIENT STRATIFICATION TO IMMUNOTHERAPY

BACKGROUND: Pediatric glioblastoma (pGBM), despite being relatively rare (incidence rate: 0.5/100,000), are a leading cause of cancer deaths in children with a median overall survival of 9–15 months. In recent years, immunotherapy has emerged as one of the more promising advances in oncology, with i...

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Autores principales: Chandramohan, Vidyalakshmi, Evangelous, Tyler, Lipp, Eric S, Hora, Bhavna, Bigner, Darell D, McLendon, Roger E, Ashley, David M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715608/
http://dx.doi.org/10.1093/neuonc/noaa222.381
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author Chandramohan, Vidyalakshmi
Evangelous, Tyler
Lipp, Eric S
Hora, Bhavna
Bigner, Darell D
McLendon, Roger E
Ashley, David M
author_facet Chandramohan, Vidyalakshmi
Evangelous, Tyler
Lipp, Eric S
Hora, Bhavna
Bigner, Darell D
McLendon, Roger E
Ashley, David M
author_sort Chandramohan, Vidyalakshmi
collection PubMed
description BACKGROUND: Pediatric glioblastoma (pGBM), despite being relatively rare (incidence rate: 0.5/100,000), are a leading cause of cancer deaths in children with a median overall survival of 9–15 months. In recent years, immunotherapy has emerged as one of the more promising advances in oncology, with impressive response rates reported in several malignancies. Effective application of immunotherapy in brain tumors depends upon a better understanding of the immune cell phenotype and mechanisms of immunosuppression in these tumors. This understanding will allow for the selection of patient population who are most likely to benefit from immunotherapeutic approaches. MATERIAL AND METHODS: In order to determine the frequency, distribution, and phenotype of tumor-infiltrating immune cells in pGBMs, we undertook an immunohistochemical survey on 19 recurrent pGBMs for CD3, CD8, CD4, CD163, PD-1, PD-L1, and FoxP3; RNA-Seq was also performed on a subset of 9 cases. Distribution of lymphocytes (LYMPHS) was recorded as intratumoral (IT) or perivascular (PV). RESULTS: The analysis indicates intratumoral CD3+ LYMPHS are commonly <5% of tumor cell mass; however, approximately half (10/19) of these recurrent pGBM have infiltrates that range from 5 to 30% CD3+ LYMPHS. Of these, 4/10 CD3+ tumors exhibit brisk CD8+ infiltrates that are associated with PD-L1+ tumor cells. These tumors with brisk CD3+/CD8+ LYMPHS and PD-L1+ tumor cells were associated with longer survivals. The data were confirmed by RNA-seq analysis. CONCLUSION: PD-L1+ pGBMs associated with CD3+/CD8+ LYMPH infiltrates deserve further investigation as candidates for immunotherapy.
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spelling pubmed-77156082020-12-09 IMMU-27. ANALYSIS OF IMMUNE SIGNATURES IN PEDIATRIC GLIOBLASTOMAS FOR PATIENT STRATIFICATION TO IMMUNOTHERAPY Chandramohan, Vidyalakshmi Evangelous, Tyler Lipp, Eric S Hora, Bhavna Bigner, Darell D McLendon, Roger E Ashley, David M Neuro Oncol Immunotherapy BACKGROUND: Pediatric glioblastoma (pGBM), despite being relatively rare (incidence rate: 0.5/100,000), are a leading cause of cancer deaths in children with a median overall survival of 9–15 months. In recent years, immunotherapy has emerged as one of the more promising advances in oncology, with impressive response rates reported in several malignancies. Effective application of immunotherapy in brain tumors depends upon a better understanding of the immune cell phenotype and mechanisms of immunosuppression in these tumors. This understanding will allow for the selection of patient population who are most likely to benefit from immunotherapeutic approaches. MATERIAL AND METHODS: In order to determine the frequency, distribution, and phenotype of tumor-infiltrating immune cells in pGBMs, we undertook an immunohistochemical survey on 19 recurrent pGBMs for CD3, CD8, CD4, CD163, PD-1, PD-L1, and FoxP3; RNA-Seq was also performed on a subset of 9 cases. Distribution of lymphocytes (LYMPHS) was recorded as intratumoral (IT) or perivascular (PV). RESULTS: The analysis indicates intratumoral CD3+ LYMPHS are commonly <5% of tumor cell mass; however, approximately half (10/19) of these recurrent pGBM have infiltrates that range from 5 to 30% CD3+ LYMPHS. Of these, 4/10 CD3+ tumors exhibit brisk CD8+ infiltrates that are associated with PD-L1+ tumor cells. These tumors with brisk CD3+/CD8+ LYMPHS and PD-L1+ tumor cells were associated with longer survivals. The data were confirmed by RNA-seq analysis. CONCLUSION: PD-L1+ pGBMs associated with CD3+/CD8+ LYMPH infiltrates deserve further investigation as candidates for immunotherapy. Oxford University Press 2020-12-04 /pmc/articles/PMC7715608/ http://dx.doi.org/10.1093/neuonc/noaa222.381 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://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 Immunotherapy
Chandramohan, Vidyalakshmi
Evangelous, Tyler
Lipp, Eric S
Hora, Bhavna
Bigner, Darell D
McLendon, Roger E
Ashley, David M
IMMU-27. ANALYSIS OF IMMUNE SIGNATURES IN PEDIATRIC GLIOBLASTOMAS FOR PATIENT STRATIFICATION TO IMMUNOTHERAPY
title IMMU-27. ANALYSIS OF IMMUNE SIGNATURES IN PEDIATRIC GLIOBLASTOMAS FOR PATIENT STRATIFICATION TO IMMUNOTHERAPY
title_full IMMU-27. ANALYSIS OF IMMUNE SIGNATURES IN PEDIATRIC GLIOBLASTOMAS FOR PATIENT STRATIFICATION TO IMMUNOTHERAPY
title_fullStr IMMU-27. ANALYSIS OF IMMUNE SIGNATURES IN PEDIATRIC GLIOBLASTOMAS FOR PATIENT STRATIFICATION TO IMMUNOTHERAPY
title_full_unstemmed IMMU-27. ANALYSIS OF IMMUNE SIGNATURES IN PEDIATRIC GLIOBLASTOMAS FOR PATIENT STRATIFICATION TO IMMUNOTHERAPY
title_short IMMU-27. ANALYSIS OF IMMUNE SIGNATURES IN PEDIATRIC GLIOBLASTOMAS FOR PATIENT STRATIFICATION TO IMMUNOTHERAPY
title_sort immu-27. analysis of immune signatures in pediatric glioblastomas for patient stratification to immunotherapy
topic Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715608/
http://dx.doi.org/10.1093/neuonc/noaa222.381
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