Journal article
Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
T-Cells and Cancer, Experimental & Translational Immunology, Department of Health Technology, Technical University of Denmark1
Experimental & Translational Immunology, Department of Health Technology, Technical University of Denmark2
Department of Health Technology, Technical University of Denmark3
Weill Cornell Medical College4
University College London5
Memorial Sloan-Kettering Cancer Center6
Technical University of Denmark7
Immunoinformatics and Machine Learning, Bioinformatics, Department of Health Technology, Technical University of Denmark8
Bioinformatics, Department of Health Technology, Technical University of Denmark9
CD8+ T cell reactivity towards tumor mutation-derived neoantigens is widely believed to facilitate the antitumor immunity induced by immune checkpoint blockade (ICB). Here we show that broadening in the number of neoantigen-reactive CD8+ T cell (NART) populations between pre-treatment to 3-weeks post-treatment distinguishes patients with controlled disease compared to patients with progressive disease in metastatic urothelial carcinoma (mUC) treated with PD-L1-blockade.
The longitudinal analysis of peripheral CD8+ T cell recognition of patient-specific neopeptide libraries consisting of DNA barcode-labelled pMHC multimers in a cohort of 24 patients from the clinical trial NCT02108652 also shows that peripheral NARTs derived from patients with disease control are characterised by a PD1+ Ki67+ effector phenotype and increased CD39 levels compared to bystander bulk- and virus-antigen reactive CD8+ T cells.
The study provides insights into NART characteristics following ICB and suggests that early-stage NART expansion and activation are associated with response to ICB in patients with mUC.
Language: | English |
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Publisher: | Nature Publishing Group UK |
Year: | 2022 |
Pages: | 1935 |
ISSN: | 20411723 |
Types: | Journal article |
DOI: | 10.1038/s41467-022-29342-0 |
ORCIDs: | 0000-0002-7235-6319 , 0000-0002-1831-6746 , 0000-0001-5381-978X , 0000-0003-1117-9272 , 0000-0002-6019-1852 , 0000-0002-6360-849X , 0000-0002-2938-6627 , 0000-0002-5093-6099 , Tamhane, Tripti , 0000-0002-1518-5111 , 0000-0001-6718-2222 , Nielsen, Morten , 0000-0003-4001-7088 , Holm, Jeppe Sejerø , Borch, Annie , Munk, Kamilla Kjærgaard , Bentzen, Amalie Kai and Hadrup, Sine Reker |