Wong, YNS;
Joshi, K;
Khetrapal, P;
Ismail, M;
Reading, JL;
Sunderland, MW;
Georgiou, A;
... Quezada, SA; + view all
(2018)
Urine-derived lymphocytes as a non-invasive measure of the bladder tumor immune microenvironment.
Journal of Experimental Medicine
, 215
(11)
pp. 2748-2759.
10.1084/jem.20181003.
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Abstract
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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