Cargando…

Complete response to PD-1 blockade following EBV-specific T-cell therapy in metastatic nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated heterogeneous disease and is characterized by peritumoral immune infiltrate. Adoptive T-cell therapy (ACT) has emerged as a potential therapeutic strategy for NPC. However, the tumor microenvironment remains a major roadblock f...

Descripción completa

Detalles Bibliográficos
Autores principales: Smith, Corey, McGrath, Margaret, Neller, Michelle A., Matthews, Katherine K., Crooks, Pauline, Le Texier, Laetitia, Panizza, Benedict, Porceddu, Sandro, Khanna, Rajiv
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979738/
https://www.ncbi.nlm.nih.gov/pubmed/33742086
http://dx.doi.org/10.1038/s41698-021-00162-7
_version_ 1783667325722951680
author Smith, Corey
McGrath, Margaret
Neller, Michelle A.
Matthews, Katherine K.
Crooks, Pauline
Le Texier, Laetitia
Panizza, Benedict
Porceddu, Sandro
Khanna, Rajiv
author_facet Smith, Corey
McGrath, Margaret
Neller, Michelle A.
Matthews, Katherine K.
Crooks, Pauline
Le Texier, Laetitia
Panizza, Benedict
Porceddu, Sandro
Khanna, Rajiv
author_sort Smith, Corey
collection PubMed
description Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated heterogeneous disease and is characterized by peritumoral immune infiltrate. Adoptive T-cell therapy (ACT) has emerged as a potential therapeutic strategy for NPC. However, the tumor microenvironment remains a major roadblock for the successful implementation of ACT in clinical settings. Expression of checkpoint molecules by malignant cells can inhibit the effector function of adoptively transferred EBV-specific T cells. Here we present a novel case report of a patient with metastatic NPC who was successfully treated with a combination of EBV-specific ACT and programmed cell death-1 blockade therapy. Following combination immunotherapy, the patient showed complete resolution of metastatic disease with no evidence of disease relapse for 22 months. Follow-up immunological analysis revealed dramatic restructuring of the global T-cell repertoire that was coincident with the clinical response. This case report provides an important platform for translating these findings to a larger cohort of NPC patients.
format Online
Article
Text
id pubmed-7979738
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-79797382021-04-12 Complete response to PD-1 blockade following EBV-specific T-cell therapy in metastatic nasopharyngeal carcinoma Smith, Corey McGrath, Margaret Neller, Michelle A. Matthews, Katherine K. Crooks, Pauline Le Texier, Laetitia Panizza, Benedict Porceddu, Sandro Khanna, Rajiv NPJ Precis Oncol Case Report Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated heterogeneous disease and is characterized by peritumoral immune infiltrate. Adoptive T-cell therapy (ACT) has emerged as a potential therapeutic strategy for NPC. However, the tumor microenvironment remains a major roadblock for the successful implementation of ACT in clinical settings. Expression of checkpoint molecules by malignant cells can inhibit the effector function of adoptively transferred EBV-specific T cells. Here we present a novel case report of a patient with metastatic NPC who was successfully treated with a combination of EBV-specific ACT and programmed cell death-1 blockade therapy. Following combination immunotherapy, the patient showed complete resolution of metastatic disease with no evidence of disease relapse for 22 months. Follow-up immunological analysis revealed dramatic restructuring of the global T-cell repertoire that was coincident with the clinical response. This case report provides an important platform for translating these findings to a larger cohort of NPC patients. Nature Publishing Group UK 2021-03-19 /pmc/articles/PMC7979738/ /pubmed/33742086 http://dx.doi.org/10.1038/s41698-021-00162-7 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Case Report
Smith, Corey
McGrath, Margaret
Neller, Michelle A.
Matthews, Katherine K.
Crooks, Pauline
Le Texier, Laetitia
Panizza, Benedict
Porceddu, Sandro
Khanna, Rajiv
Complete response to PD-1 blockade following EBV-specific T-cell therapy in metastatic nasopharyngeal carcinoma
title Complete response to PD-1 blockade following EBV-specific T-cell therapy in metastatic nasopharyngeal carcinoma
title_full Complete response to PD-1 blockade following EBV-specific T-cell therapy in metastatic nasopharyngeal carcinoma
title_fullStr Complete response to PD-1 blockade following EBV-specific T-cell therapy in metastatic nasopharyngeal carcinoma
title_full_unstemmed Complete response to PD-1 blockade following EBV-specific T-cell therapy in metastatic nasopharyngeal carcinoma
title_short Complete response to PD-1 blockade following EBV-specific T-cell therapy in metastatic nasopharyngeal carcinoma
title_sort complete response to pd-1 blockade following ebv-specific t-cell therapy in metastatic nasopharyngeal carcinoma
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979738/
https://www.ncbi.nlm.nih.gov/pubmed/33742086
http://dx.doi.org/10.1038/s41698-021-00162-7
work_keys_str_mv AT smithcorey completeresponsetopd1blockadefollowingebvspecifictcelltherapyinmetastaticnasopharyngealcarcinoma
AT mcgrathmargaret completeresponsetopd1blockadefollowingebvspecifictcelltherapyinmetastaticnasopharyngealcarcinoma
AT nellermichellea completeresponsetopd1blockadefollowingebvspecifictcelltherapyinmetastaticnasopharyngealcarcinoma
AT matthewskatherinek completeresponsetopd1blockadefollowingebvspecifictcelltherapyinmetastaticnasopharyngealcarcinoma
AT crookspauline completeresponsetopd1blockadefollowingebvspecifictcelltherapyinmetastaticnasopharyngealcarcinoma
AT letexierlaetitia completeresponsetopd1blockadefollowingebvspecifictcelltherapyinmetastaticnasopharyngealcarcinoma
AT panizzabenedict completeresponsetopd1blockadefollowingebvspecifictcelltherapyinmetastaticnasopharyngealcarcinoma
AT porceddusandro completeresponsetopd1blockadefollowingebvspecifictcelltherapyinmetastaticnasopharyngealcarcinoma
AT khannarajiv completeresponsetopd1blockadefollowingebvspecifictcelltherapyinmetastaticnasopharyngealcarcinoma