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Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood
Efficacy of checkpoint inhibitor therapies in cancer varies greatly, with some patients showing complete responses while others do not respond and experience progressive disease. We aimed to identify correlates of response and progression following PD-1-directed therapy by immunophenotyping peripher...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9929715/ https://www.ncbi.nlm.nih.gov/pubmed/36818683 http://dx.doi.org/10.1093/immadv/ltad001 |
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author | Edner, Natalie M Ntavli, Elisavet Petersone, Lina Wang, Chun Jing Fabri, Astrid Kogimtzis, Alexandros Ovcinnikovs, Vitalijs Ross, Ellen M Heuts, Frank Elfaki, Yassin Houghton, Luke P Talbot, Toby Sheri, Amna Pender, Alexandra Chao, David Walker, Lucy S K |
author_facet | Edner, Natalie M Ntavli, Elisavet Petersone, Lina Wang, Chun Jing Fabri, Astrid Kogimtzis, Alexandros Ovcinnikovs, Vitalijs Ross, Ellen M Heuts, Frank Elfaki, Yassin Houghton, Luke P Talbot, Toby Sheri, Amna Pender, Alexandra Chao, David Walker, Lucy S K |
author_sort | Edner, Natalie M |
collection | PubMed |
description | Efficacy of checkpoint inhibitor therapies in cancer varies greatly, with some patients showing complete responses while others do not respond and experience progressive disease. We aimed to identify correlates of response and progression following PD-1-directed therapy by immunophenotyping peripheral blood samples from 20 patients with advanced malignant melanoma before and after treatment with the PD-1 blocking antibody pembrolizumab. Our data reveal that individuals responding to PD-1 blockade were characterised by increased CD8 T cell proliferation following treatment, while progression was associated with an increase in CTLA-4-expressing Treg. Remarkably, unsupervised clustering analysis of pre-treatment T cell subsets revealed differences in individuals that went on to respond to PD-1 blockade compared to individuals that did not. These differences mapped to expression of the proliferation marker Ki67 and the costimulatory receptor CD28 as well as the inhibitory molecules 2B4 and KLRG1. While these results require validation in larger patient cohorts, they suggest that flow cytometric analysis of a relatively small number of T cell markers in peripheral blood could potentially allow stratification of PD-1 blockade treatment response prior to therapy initiation. |
format | Online Article Text |
id | pubmed-9929715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-99297152023-02-16 Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood Edner, Natalie M Ntavli, Elisavet Petersone, Lina Wang, Chun Jing Fabri, Astrid Kogimtzis, Alexandros Ovcinnikovs, Vitalijs Ross, Ellen M Heuts, Frank Elfaki, Yassin Houghton, Luke P Talbot, Toby Sheri, Amna Pender, Alexandra Chao, David Walker, Lucy S K Immunother Adv Immunotherapy of Asthma and Allergy Efficacy of checkpoint inhibitor therapies in cancer varies greatly, with some patients showing complete responses while others do not respond and experience progressive disease. We aimed to identify correlates of response and progression following PD-1-directed therapy by immunophenotyping peripheral blood samples from 20 patients with advanced malignant melanoma before and after treatment with the PD-1 blocking antibody pembrolizumab. Our data reveal that individuals responding to PD-1 blockade were characterised by increased CD8 T cell proliferation following treatment, while progression was associated with an increase in CTLA-4-expressing Treg. Remarkably, unsupervised clustering analysis of pre-treatment T cell subsets revealed differences in individuals that went on to respond to PD-1 blockade compared to individuals that did not. These differences mapped to expression of the proliferation marker Ki67 and the costimulatory receptor CD28 as well as the inhibitory molecules 2B4 and KLRG1. While these results require validation in larger patient cohorts, they suggest that flow cytometric analysis of a relatively small number of T cell markers in peripheral blood could potentially allow stratification of PD-1 blockade treatment response prior to therapy initiation. Oxford University Press 2023-01-06 /pmc/articles/PMC9929715/ /pubmed/36818683 http://dx.doi.org/10.1093/immadv/ltad001 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Immunotherapy of Asthma and Allergy Edner, Natalie M Ntavli, Elisavet Petersone, Lina Wang, Chun Jing Fabri, Astrid Kogimtzis, Alexandros Ovcinnikovs, Vitalijs Ross, Ellen M Heuts, Frank Elfaki, Yassin Houghton, Luke P Talbot, Toby Sheri, Amna Pender, Alexandra Chao, David Walker, Lucy S K Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood |
title | Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood |
title_full | Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood |
title_fullStr | Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood |
title_full_unstemmed | Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood |
title_short | Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood |
title_sort | stratification of pd-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood |
topic | Immunotherapy of Asthma and Allergy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9929715/ https://www.ncbi.nlm.nih.gov/pubmed/36818683 http://dx.doi.org/10.1093/immadv/ltad001 |
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