Urine-derived lymphocytes as a non-invasive measure of the bladder tumor immune microenvironment.
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Date
2018-11-05Author
Wong, YNS
Joshi, K
Khetrapal, P
Ismail, M
Reading, JL
Sunderland, MW
Georgiou, A
Furness, AJS
Ben Aissa, A
Ghorani, E
Oakes, T
Uddin, I
Tan, WS
Feber, A
McGovern, U
Swanton, C
Freeman, A
Marafioti, T
Briggs, TP
Kelly, JD
Powles, T
Peggs, KS
Chain, BM
Linch, MD
Quezada, SA
Type
Journal Article
Metadata
Show full item recordAbstract
Despite the advances in cancer immunotherapy, only a fraction of patients with bladder cancer exhibit responses to checkpoint blockade, highlighting a need to better understand drug resistance and identify rational immunotherapy combinations. However, accessibility to the tumor prior and during therapy is a major limitation in understanding the immune tumor microenvironment (TME). Herein, we identified urine-derived lymphocytes (UDLs) as a readily accessible source of T cells in 32 patients with muscle invasive bladder cancer (MIBC). We observed that effector CD8+ and CD4+ cells and regulatory T cells within the urine accurately map the immune checkpoint landscape and T cell receptor repertoire of the TME. Finally, an increased UDL count, specifically high expression of PD-1 (PD-1hi) on CD8+ at the time of cystectomy, was associated with a shorter recurrence-free survival. UDL analysis represents a dynamic liquid biopsy that is representative of the bladder immune TME that may be used to identify actionable immuno-oncology (IO) targets with potential prognostic value in MIBC.
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Subject
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Urine
Humans
Lymphocyte Count
Female
Male
Urinary Bladder Neoplasms
Tumor Microenvironment
Language
eng
Date accepted
2018-09-05
License start date
2018-11
Citation
The Journal of experimental medicine, 2018, 215 (11), pp. 2748 - 2759
Publisher
ROCKEFELLER UNIV PRESS