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Volume 221, Issue 8
5 August 2024
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Technical Advances and Resources| June 07 2024
Michelle A. Tran
,
Michelle A. Tran
(Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Software, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Division of Hematology and Medical Oncology,
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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Dina Youssef
,
Dina Youssef
(Data curation, Investigation)
1Division of Hematology and Medical Oncology,
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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Sanjana Shroff
,
Sanjana Shroff
(Data curation, Investigation)
2Department of Genomics,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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Disha Chowhan
,
Disha Chowhan
(Data curation, Investigation)
2Department of Genomics,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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Kristin G. Beaumont
,
Kristin G. Beaumont
(Investigation, Methodology, Project administration, Supervision, Writing - review & editing)
2Department of Genomics,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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Robert Sebra
,
Robert Sebra
(Investigation, Methodology, Resources, Writing - review & editing)
2Department of Genomics,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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Reza Mehrazin
,
Reza Mehrazin
(Resources, Writing - review & editing)
3Department of Urology,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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Peter Wiklund
,
Peter Wiklund
(Investigation, Resources)
3Department of Urology,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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Jenny J. Lin
,
Jenny J. Lin
(Resources, Writing - review & editing)
4Department of Medicine,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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Amir Horowitz
,
Amir Horowitz
(Resources, Writing - review & editing)
5Department of Immunology and Immunotherapy,
The Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
6Department of Oncological Sciences,
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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Adam M. Farkas
,
Adam M. Farkas *
(Conceptualization, Funding acquisition, Methodology, Supervision, Writing - review & editing)
1Division of Hematology and Medical Oncology,
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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Matthew D. Galsky
,
Matthew D. Galsky *
(Funding acquisition, Investigation, Writing - review & editing)
1Division of Hematology and Medical Oncology,
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
3Department of Urology,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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John P. Sfakianos
,
John P. Sfakianos *
(Funding acquisition, Resources, Supervision, Writing - review & editing)
3Department of Urology,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
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Nina Bhardwaj
Nina Bhardwaj *
(Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing - review & editing)
1Division of Hematology and Medical Oncology,
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
3Department of Urology,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
7
Extramural Member, Parker Institute for Cancer Immunotherapy
, San Francisco, CA,
USA
Correspondence to Nina Bhardwaj: nina.bhardwaj@mssm.edu
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Author and Article Information
Michelle A. Tran
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Software, Validation, Visualization, Writing - original draft, Writing - review & editing
1Division of Hematology and Medical Oncology,
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
1Division of Hematology and Medical Oncology,
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
2Department of Genomics,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
2Department of Genomics,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
Kristin G. Beaumont
Investigation, Methodology, Project administration, Supervision, Writing - review & editing
2Department of Genomics,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
Robert Sebra
Investigation, Methodology, Resources, Writing - review & editing
2Department of Genomics,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
3Department of Urology,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
3Department of Urology,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
4Department of Medicine,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
5Department of Immunology and Immunotherapy,
The Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
6Department of Oncological Sciences,
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
Adam M. Farkas
Conceptualization, Funding acquisition, Methodology, Supervision, Writing - review & editing *
1Division of Hematology and Medical Oncology,
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
Matthew D. Galsky
Funding acquisition, Investigation, Writing - review & editing *
1Division of Hematology and Medical Oncology,
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
3Department of Urology,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
John P. Sfakianos
Funding acquisition, Resources, Supervision, Writing - review & editing *
3Department of Urology,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
Nina Bhardwaj
Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing - review & editing *
1Division of Hematology and Medical Oncology,
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
3Department of Urology,
Icahn School of Medicine at Mount Sinai
, New York, NY,
USA
7
Extramural Member, Parker Institute for Cancer Immunotherapy
, San Francisco, CA,
USA
Correspondence to Nina Bhardwaj: nina.bhardwaj@mssm.edu
*
A.M. Farkas, M.D. Galsky, J.P. Sfakianos, and N. Bhardwaj contributed equally to this paper.
Disclosures: R. Sebra reported being a paid consultant with GeneDx, unrelated to the submitted work. M.D. Galsky reported personal fees from Bristol Myers, Merck, Genentech, Astra Zeneca, Pfizer, EMD Serono, Seagen, Janssen, Numab, Dragonfly, Glaxo Smith Kline, Basilea, Urogen, Rappta Therapeutics, Alligator, Silverback, Fujifilm, Curis, Gilead, Bicycle, Asieris, Abbvie, Analog Devices, and Veracyte outside the submitted work; consultancy in BioMotiv, Astellas, Inctye, Dracen, Inovio, Aileron; and grants from Dendreon and Novartis. N. Bhardwaj reported “other” from DC Prime and Vaccitech and grants from Merck outside the submitted work. In addition, N. Bhardwaj receives research support from Dragonfly Therapeutics, Harbour Biomed, and Regeneron and is a consultant, advisor, or board member for Apricity, BreakBio, Carisma Therapeutics, CureVac, Genentech, Genotwin, Novartis, Primevax, Rome Therapeutics, Tempest Therapeutics, and ATP. A. Horowitz receives research funding from Astra Zeneca and has served on advisory boards for Purple Biotech and UroGen. J.P. Sfakianos reports consultancy in Pacific Edge, Natera, and Merck. No other disclosures were reported.
Received: January 07 2024
Revision Received: April 04 2024
Accepted: May 21 2024
Online ISSN: 1540-9538
Print ISSN: 0022-1007
Funding
Funder(s):
Department of Defense
- Award Id(s):
TTSA CA181008
Funder(s):
Cancer Research Institute
- Award Id(s):
CRI4377
© 2024 Tran et al.
2024
Tran et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Exp Med (2024) 221 (8): e20240045.
Article history
Received:
January 07 2024
Revision Received:
April 04 2024
Accepted:
May 21 2024
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Citation
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; Urine scRNAseq reveals new insights into the bladder tumor immune microenvironment. J Exp Med 5 August 2024; 221 (8): e20240045. doi: https://doi.org/10.1084/jem.20240045
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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.
Subjects:
Solid tumors, Tumor immunology
© 2024 Tran et al.
2024
Tran et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
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