Article ; Online: Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood.
Immunotherapy advances
2023 Volume 3, Issue 1, Page(s) ltad001
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- ... ...
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. |
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Language | English |
Publishing date | 2023-01-06 |
Publishing country | England |
Document type | Journal Article |
ISSN | 2732-4303 |
ISSN (online) | 2732-4303 |
DOI | 10.1093/immadv/ltad001 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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