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.
The Journal of experimental medicine. 2018 Sep 26 [Epub]
Yien Ning Sophia Wong, Kroopa Joshi, Pramit Khetrapal, Mazlina Ismail, James L Reading, Mariana Werner Sunderland, Andrew Georgiou, Andrew J S Furness, Assma Ben Aissa, Ehsan Ghorani, Theres Oakes, Imran Uddin, Wei Shen Tan, Andrew Feber, Ursula McGovern, Charles Swanton, Alex Freeman, Teresa Marafioti, Timothy P Briggs, John D Kelly, Thomas Powles, Karl S Peggs, Benjamin M Chain, Mark D Linch, Sergio A Quezada
Cancer Immunology Unit, University College London (UCL) Cancer Institute, London, England, UK., Department of Urology, University College London Hospital at Westmoreland Street, London, England, UK., Division of Infection and Immunity, University College London, London, England, UK., Division of Surgical and Interventional Sciences, University College London, London, England, UK., Department of Oncology, University College London Hospital, London, England, UK., The Francis Crick Institute, London, England, UK., Department of Cellular Pathology, University College London Hospital, London, England, UK., Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, England, UK., Department of Oncology, UCL Cancer Institute, London, England, UK ., Cancer Immunology Unit, University College London (UCL) Cancer Institute, London, England, UK .