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Durable benefit and change in TCR clonality with nivolumab in a Lynch syndrome–associated glioma
Germline replication-repair deficient (gRRD) gliomas are exceptional events, and only a few of them have been treated with immune checkpoint inhibitors (ICIs). Contrary to sporadic gliomas, where ICIs have failed to show any objective benefit, the very few patients with gRRD gliomas treated with ICI...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185004/ https://www.ncbi.nlm.nih.gov/pubmed/35694191 http://dx.doi.org/10.1177/17588359221100863 |
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author | Cabezas-Camarero, Santiago Pérez-Alfayate, Rebeca García-Barberán, Vanesa Polidura, María Carmen Gómez-Ruiz, María Natividad Casado-Fariñas, Isabel Subhi-Issa, Issa Ahmad Hernández, José Carlos Plaza Garre, Pilar Díaz-Millán, Isabel Pérez-Segura, Pedro |
author_facet | Cabezas-Camarero, Santiago Pérez-Alfayate, Rebeca García-Barberán, Vanesa Polidura, María Carmen Gómez-Ruiz, María Natividad Casado-Fariñas, Isabel Subhi-Issa, Issa Ahmad Hernández, José Carlos Plaza Garre, Pilar Díaz-Millán, Isabel Pérez-Segura, Pedro |
author_sort | Cabezas-Camarero, Santiago |
collection | PubMed |
description | Germline replication-repair deficient (gRRD) gliomas are exceptional events, and only a few of them have been treated with immune checkpoint inhibitors (ICIs). Contrary to sporadic gliomas, where ICIs have failed to show any objective benefit, the very few patients with gRRD gliomas treated with ICIs to date seem to benefit from programmed-death-1 (PD-1) inhibitors, such as nivolumab or pembrolizumab, either in terms of durable responses or in terms of survival. T-cell immunohistochemistry (IHC) and T-cell receptor (TCR) repertoire using high-throughput next-generation sequencing (NGS) with the Oncomine TCR-Beta-SR assay (Thermo Fisher Scientific) were analyzed in pre- and post-nivolumab tumor biopsies obtained from a patient with a Lynch syndrome-associated glioma due to a germline pathogenic hMLH1 mutation. The aim was to describe changes in the T-cell quantity and clonality after treatment with nivolumab to better understand the role of acquired immunity in gRRD gliomas. The patient showed a slow disease progression and overall survival of 10 months since the start of anti-PD-1 therapy with excellent tolerance. A very scant T-cell infiltrate was observed both at initial diagnosis and after four cycles of nivolumab. The drastic change observed in TCR clonality in the post-nivolumab biopsy may be explained by the highly spatial and temporal heterogeneity of glioblastomas. Despite the durable benefit from nivolumab, the scant T-cell infiltrate possibly explains the lack of objective response to anti-PD-1 therapy. The major change in TCR clonality observed after nivolumab possibly reflects the evolving molecular heterogeneity in a highly pre-treated disease. An in-deep review of the available literature regarding the role of ICIs in both sporadic and gRRD gliomas was conducted. |
format | Online Article Text |
id | pubmed-9185004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-91850042022-06-11 Durable benefit and change in TCR clonality with nivolumab in a Lynch syndrome–associated glioma Cabezas-Camarero, Santiago Pérez-Alfayate, Rebeca García-Barberán, Vanesa Polidura, María Carmen Gómez-Ruiz, María Natividad Casado-Fariñas, Isabel Subhi-Issa, Issa Ahmad Hernández, José Carlos Plaza Garre, Pilar Díaz-Millán, Isabel Pérez-Segura, Pedro Ther Adv Med Oncol Case Report Germline replication-repair deficient (gRRD) gliomas are exceptional events, and only a few of them have been treated with immune checkpoint inhibitors (ICIs). Contrary to sporadic gliomas, where ICIs have failed to show any objective benefit, the very few patients with gRRD gliomas treated with ICIs to date seem to benefit from programmed-death-1 (PD-1) inhibitors, such as nivolumab or pembrolizumab, either in terms of durable responses or in terms of survival. T-cell immunohistochemistry (IHC) and T-cell receptor (TCR) repertoire using high-throughput next-generation sequencing (NGS) with the Oncomine TCR-Beta-SR assay (Thermo Fisher Scientific) were analyzed in pre- and post-nivolumab tumor biopsies obtained from a patient with a Lynch syndrome-associated glioma due to a germline pathogenic hMLH1 mutation. The aim was to describe changes in the T-cell quantity and clonality after treatment with nivolumab to better understand the role of acquired immunity in gRRD gliomas. The patient showed a slow disease progression and overall survival of 10 months since the start of anti-PD-1 therapy with excellent tolerance. A very scant T-cell infiltrate was observed both at initial diagnosis and after four cycles of nivolumab. The drastic change observed in TCR clonality in the post-nivolumab biopsy may be explained by the highly spatial and temporal heterogeneity of glioblastomas. Despite the durable benefit from nivolumab, the scant T-cell infiltrate possibly explains the lack of objective response to anti-PD-1 therapy. The major change in TCR clonality observed after nivolumab possibly reflects the evolving molecular heterogeneity in a highly pre-treated disease. An in-deep review of the available literature regarding the role of ICIs in both sporadic and gRRD gliomas was conducted. SAGE Publications 2022-06-08 /pmc/articles/PMC9185004/ /pubmed/35694191 http://dx.doi.org/10.1177/17588359221100863 Text en © The Author(s), 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Case Report Cabezas-Camarero, Santiago Pérez-Alfayate, Rebeca García-Barberán, Vanesa Polidura, María Carmen Gómez-Ruiz, María Natividad Casado-Fariñas, Isabel Subhi-Issa, Issa Ahmad Hernández, José Carlos Plaza Garre, Pilar Díaz-Millán, Isabel Pérez-Segura, Pedro Durable benefit and change in TCR clonality with nivolumab in a Lynch syndrome–associated glioma |
title | Durable benefit and change in TCR clonality with nivolumab in a Lynch
syndrome–associated glioma |
title_full | Durable benefit and change in TCR clonality with nivolumab in a Lynch
syndrome–associated glioma |
title_fullStr | Durable benefit and change in TCR clonality with nivolumab in a Lynch
syndrome–associated glioma |
title_full_unstemmed | Durable benefit and change in TCR clonality with nivolumab in a Lynch
syndrome–associated glioma |
title_short | Durable benefit and change in TCR clonality with nivolumab in a Lynch
syndrome–associated glioma |
title_sort | durable benefit and change in tcr clonality with nivolumab in a lynch
syndrome–associated glioma |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185004/ https://www.ncbi.nlm.nih.gov/pubmed/35694191 http://dx.doi.org/10.1177/17588359221100863 |
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