Due to bladder tumors' contact with urine, urine-derived cells (UDCs) may serve as a surrogate for monitoring the tumor microenvironment (TME) in bladder cancer (BC). However, the composition of UDCs and the extent to which they mirror the tumor remain poorly characterized. We generated the first single-cell RNA-sequencing of BC patient UDCs with matched tumor and peripheral blood mononuclear cells (PBMC). BC urine was more cellular than healthy donor (HD) urine, containing multiple immune populations including myeloid cells, CD4+ and CD8+ T cells, natural killer (NK) cells, B cells, and dendritic cells (DCs) in addition to tumor and stromal cells. Immune UDCs were transcriptionally more similar to tumor than blood. UDCs encompassed cytotoxic and activated CD4+ T cells, exhausted and tissue-resident memory CD8+ T cells, macrophages, germinal-center-like B cells, tissue-resident and adaptive NK cells, and regulatory DCs found in tumor but lacking or absent in blood. Our findings suggest BC UDCs may be surrogates for the TME and serve as therapeutic biomarkers.
The Journal of experimental medicine. 2024 Jun 07 [Epub]
Michelle A Tran, Dina Youssef, Sanjana Shroff, Disha Chowhan, Kristin G Beaumont, Robert Sebra, Reza Mehrazin, Peter Wiklund, Jenny J Lin, Amir Horowitz, Adam M Farkas, Matthew D Galsky, John P Sfakianos, Nina Bhardwaj
Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Department of Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Department of Immunology and Immunotherapy, The Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.