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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
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.
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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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