Synapse - Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma

Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma Journal Article

Authors:	Holm, J. S.; Funt, S. A.; Borch, A.; Munk, K. K.; Bjerregaard, A. M.; Reading, J. L.; Maher, C.; Regazzi, A.; Wong, P.; Al-Ahmadie, H.; Iyer, G.; Tamhane, T.; Bentzen, A. K.; Herschend, N. O.; De Wolf, S.; Snyder, A.; Merghoub, T.; Wolchok, J. D.; Nielsen, M.; Rosenberg, J. E.; Bajorin, D. F.; Hadrup, S. R.
Article Title:	Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
Abstract:	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. © 2022, The Author(s).
Keywords:	genetics; cd8+ t lymphocyte; cd8-positive t-lymphocytes; phenotype; bladder tumor; urinary bladder neoplasms; dna; immunity; tumor; disease control; carcinoma, transitional cell; recognition; transitional cell carcinoma; programmed death 1 ligand 1; expansion; humans; human; immune checkpoint inhibitors; b7-h1 antigen
Journal Title:	Nature Communications
Volume:	13
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2022-04-11
Start Page:	1935
Language:	English
DOI:	10.1038/s41467-022-29342-0
PUBMED:	35410325
PROVIDER:	scopus
PMCID:	PMC9001725
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85128040501&doi=10.1038%2fs41467-022-29342-0&partnerID=40&md5=7a4bc91b44b2d72ebf94db99dbae1cc3
Notes:	Article -- Export Date: 2 May 2022 -- Source: Scopus