Edner, Natalie M;
Ntavli, Elisavet;
Petersone, Lina;
Wang, Chun Jing;
Fabri, Astrid;
Kogimtzis, Alexandros;
Ovcinnikovs, Vitalijs;
... Walker, Lucy SK; + view all
(2023)
Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood.
Immunotherapy Advances
, 3
(1)
, Article ltad001. 10.1093/immadv/ltad001.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/immadv/ltad001 |
| Publisher version: | https://doi.org/10.1093/immadv/ltad001 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | PD-1 blockade, biomarker research, checkpoint inhibition, immunotherapy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10165816 |
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