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Squamous Cell Carcinomas of the Head and Neck Cancer Response to Programmed Cell Death Protein-1 Targeting and Differential Expression of Immunological Markers: A Case Report
Targeting the programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway has been shown to enhance T cell-mediated antitumor immunity. Clinical responses are limited to subgroups of patients. The search for biomarkers of response is a strategy to predict response and outcome of PD-1/PD-L1 ch...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079623/ https://www.ncbi.nlm.nih.gov/pubmed/30108590 http://dx.doi.org/10.3389/fimmu.2018.01769 |
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author | Merhi, Maysaloun Raza, Afsheen Inchakalody, Varghese Philipose Nashwan, Abdulqadir Jeprel Japer Allahverdi, Niloofar Krishnankutty, Roopesh Uddin, Shahab Zar Gul, Abdul Rehman Al Homsi, Mohammed Ussama Dermime, Said |
author_facet | Merhi, Maysaloun Raza, Afsheen Inchakalody, Varghese Philipose Nashwan, Abdulqadir Jeprel Japer Allahverdi, Niloofar Krishnankutty, Roopesh Uddin, Shahab Zar Gul, Abdul Rehman Al Homsi, Mohammed Ussama Dermime, Said |
author_sort | Merhi, Maysaloun |
collection | PubMed |
description | Targeting the programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway has been shown to enhance T cell-mediated antitumor immunity. Clinical responses are limited to subgroups of patients. The search for biomarkers of response is a strategy to predict response and outcome of PD-1/PD-L1 checkpoint intervention. The NY-ESO-1 cancer testis antigen has been considered as a biomarker in head and neck squamous cell carcinoma (HNSCC) patients and can induce both specific NY-ESO-1 antibody and T cells responses. Here, we correlated clinical responsiveness to anti-PD-1 (nivolumab) treatment with immunity to NY-ESO-1 in a patient with recurrent HNSCC. The patient was treated with second-line treatment of nivolumab and had a stable disease for over 7 months. His NY-ESO-1 antibody was found to be lower after the third (****p < 0.0001) and the fifth (****p < 0.0001) cycles of treatment compared to base line, and this was in line with the stability of the disease. The NY-ESO-1-specific T cells response of the patient was found to be increased after the third and the fifth (**p = 0.002) cycles of treatment but had a significant decline after progression (**p = 0.0028). The PD-1 expression by the patient’s T cells was reduced 15-folds after nivolumab treatment and was uniquely restricted to the CD8(+) T cells population. Several cytokines/chemokines involved in immune activation were upregulated after nivolumab treatment; two biomarkers were reduced at progression [interleukin (IL)-10: ****p < 0.0001 and CX3CL1: ****p < 0.0001]. On the other hand, some cytokines/chemokines contributing to immune inhibition were downregulated after nivolumab treatment; two biomarkers were increased at progression (IL-6: ****p < 0.0001 and IL-8: ****p < 0.0001). This data support the notion that the presence of anti-NY-ESO-1 integrated immunity and some cytokines/chemokines profile may potentially identify a response to PD-1 blockade in HNSCC patients. |
format | Online Article Text |
id | pubmed-6079623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60796232018-08-14 Squamous Cell Carcinomas of the Head and Neck Cancer Response to Programmed Cell Death Protein-1 Targeting and Differential Expression of Immunological Markers: A Case Report Merhi, Maysaloun Raza, Afsheen Inchakalody, Varghese Philipose Nashwan, Abdulqadir Jeprel Japer Allahverdi, Niloofar Krishnankutty, Roopesh Uddin, Shahab Zar Gul, Abdul Rehman Al Homsi, Mohammed Ussama Dermime, Said Front Immunol Immunology Targeting the programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway has been shown to enhance T cell-mediated antitumor immunity. Clinical responses are limited to subgroups of patients. The search for biomarkers of response is a strategy to predict response and outcome of PD-1/PD-L1 checkpoint intervention. The NY-ESO-1 cancer testis antigen has been considered as a biomarker in head and neck squamous cell carcinoma (HNSCC) patients and can induce both specific NY-ESO-1 antibody and T cells responses. Here, we correlated clinical responsiveness to anti-PD-1 (nivolumab) treatment with immunity to NY-ESO-1 in a patient with recurrent HNSCC. The patient was treated with second-line treatment of nivolumab and had a stable disease for over 7 months. His NY-ESO-1 antibody was found to be lower after the third (****p < 0.0001) and the fifth (****p < 0.0001) cycles of treatment compared to base line, and this was in line with the stability of the disease. The NY-ESO-1-specific T cells response of the patient was found to be increased after the third and the fifth (**p = 0.002) cycles of treatment but had a significant decline after progression (**p = 0.0028). The PD-1 expression by the patient’s T cells was reduced 15-folds after nivolumab treatment and was uniquely restricted to the CD8(+) T cells population. Several cytokines/chemokines involved in immune activation were upregulated after nivolumab treatment; two biomarkers were reduced at progression [interleukin (IL)-10: ****p < 0.0001 and CX3CL1: ****p < 0.0001]. On the other hand, some cytokines/chemokines contributing to immune inhibition were downregulated after nivolumab treatment; two biomarkers were increased at progression (IL-6: ****p < 0.0001 and IL-8: ****p < 0.0001). This data support the notion that the presence of anti-NY-ESO-1 integrated immunity and some cytokines/chemokines profile may potentially identify a response to PD-1 blockade in HNSCC patients. Frontiers Media S.A. 2018-07-30 /pmc/articles/PMC6079623/ /pubmed/30108590 http://dx.doi.org/10.3389/fimmu.2018.01769 Text en Copyright © 2018 Merhi, Raza, Inchakalody, Nashwan, Allahverdi, Krishnankutty, Uddin, Zar Gul, Al Homsi and Dermime. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Merhi, Maysaloun Raza, Afsheen Inchakalody, Varghese Philipose Nashwan, Abdulqadir Jeprel Japer Allahverdi, Niloofar Krishnankutty, Roopesh Uddin, Shahab Zar Gul, Abdul Rehman Al Homsi, Mohammed Ussama Dermime, Said Squamous Cell Carcinomas of the Head and Neck Cancer Response to Programmed Cell Death Protein-1 Targeting and Differential Expression of Immunological Markers: A Case Report |
title | Squamous Cell Carcinomas of the Head and Neck Cancer Response to Programmed Cell Death Protein-1 Targeting and Differential Expression of Immunological Markers: A Case Report |
title_full | Squamous Cell Carcinomas of the Head and Neck Cancer Response to Programmed Cell Death Protein-1 Targeting and Differential Expression of Immunological Markers: A Case Report |
title_fullStr | Squamous Cell Carcinomas of the Head and Neck Cancer Response to Programmed Cell Death Protein-1 Targeting and Differential Expression of Immunological Markers: A Case Report |
title_full_unstemmed | Squamous Cell Carcinomas of the Head and Neck Cancer Response to Programmed Cell Death Protein-1 Targeting and Differential Expression of Immunological Markers: A Case Report |
title_short | Squamous Cell Carcinomas of the Head and Neck Cancer Response to Programmed Cell Death Protein-1 Targeting and Differential Expression of Immunological Markers: A Case Report |
title_sort | squamous cell carcinomas of the head and neck cancer response to programmed cell death protein-1 targeting and differential expression of immunological markers: a case report |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079623/ https://www.ncbi.nlm.nih.gov/pubmed/30108590 http://dx.doi.org/10.3389/fimmu.2018.01769 |
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