T cells in the urine of bladder cancer patients reflect tumor environment

Liquid biopsies could help monitor treatment

Scientists in the UK have shown for the first time that immune cells in the urine of bladder cancer patients accurately reflect those in the tumor environment, according to the study “Urine-derived lymphocytes as a non-invasive measure of the bladder tumor immune microenvironment,” by Wong et al., published today in the Journal of Experimental Medicine.

Unexpectedly, the Cancer Research UK-funded study showed that immune cells found in the urine were more representative of the tumor than immune cells from the blood, suggesting that urine, rather than blood liquid biopsies, could help to more accurately monitor response to immunotherapy in patients.

Immunotherapy has shown success in patients with advanced bladder cancer and is approved in the UK and US for certain patients.* Despite this, only around a quarter of patients in the UK respond to immune checkpoint-targeting drugs, demonstrating a pressing need to better understand the immune landscape of bladder cancer and develop new therapeutics.

The study, which was also supported by the National Institute for Health Research, looked at 32 patients with bladder cancer that had invaded the muscle wall. Urine and blood samples were taken on the day of surgery to remove their tumor, and these were compared with both their tumor and healthy bladder tissue.

The researchers at University College London (UCL) Cancer Institute and UCL Hospitals were able to identify T cells in the urine, which are usually absent in healthy individuals. Crucially, the T cells matched those found within the tumor environment of the bladder cancer, regardless of cancer stage and treatment history. This included the checkpoint molecules PD-1 and CTLA-4, which are targeted by approved immunotherapy drugs, and others such as TIM-3 which are being evaluated in early clinical trials.

Dr Sophia Wong, co-lead author from UCL, said: “Our results show for the first time that urine liquid biopsies can be used as a non-invasive window into the bladder tumor environment. This valuable information could be used to discover immunotherapy targets and aid the design of combination treatments that exploit different components of the immune system.

“This research looked at a single time point, so clinical trials that include urine analysis over time are now needed to find out whether urine-derived T cells could tell us if a patient is responding to treatment, or be an early warning that a switch in therapy is required.”

The study also identified a relationship between urine-derived T cells and patients’ chance of survival, as the disease was more likely to return in people with higher numbers of these cells. This indicates that urine-derived T cells may therefore also serve as a prognostic marker.

There are around 10,300 people in the UK diagnosed with bladder cancer every year. And it can be difficult to treat; just more than half (53%) of patients survive their disease for 5 years or more. Annually in the US, about 72,000 men and women get bladder cancer, and 16,000 die from the disease.

Professor Peter Johnson, an immunotherapy expert at the Cancer Research UK Southampton Centre, said: “Immunotherapy holds great promise for cancers that are difficult to treat, but a greater knowledge of the complex immune system is required to unlock their potential. By using a non-invasive urine test to profile the bladder cancer immune landscape, this small study could help us understand why only a fraction of patients respond to immunotherapy.

“If the findings are supported by larger studies, this early research suggests that urine liquid biopsies could one day help stratify patients for immunotherapy, identifying those most likely to benefit, while sparing unnecessary treatment in those who likely won’t.”


Wong et al., 2018. J. Exp. Med. Please note: The corresponding research article will be freely accessible for two weeks from the date of publication at http://jem.rupress.org/content/early/2018/09/25/jem.20181003?PR

*In the UK, Pembrolizumab (Keytruda) and atezolizumab (Tecentriq) are available through the Cancer Drugs Fund for some patients with locally advanced or metastatic bladder cancer. It should be noted that the U.S. Food and Drug Administration has limited the use of Tecentriq and Keytruda for patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing therapy.

Text provided by the Cancer Research UK press office. To reach the authors, contact Dr. Justine Alford at 020-3469-8456, 07050-264-059 (after hours), Justine.Alford@cancer.org.uk.

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