Mapping the immune environment in clear cell renal carcinoma by single-cell genomics

Nicholas Borcherding; Ajaykumar Vishwakarma; Andrew P Voigt; Andrew Bellizzi; Jacob Kaplan; Kenneth Nepple; Aliasger K Salem; Russell W Jenkins; Yousef Zakharia; Weizhou Zhang

doi:10.1038/s42003-020-01625-6

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Mapping the immune environment in clear cell renal carcinoma by single-cell genomics

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Mapping the immune environment in clear cell renal carcinoma by single-cell genomics

Nicholas Borcherding, Ajaykumar Vishwakarma, Andrew P Voigt, Andrew Bellizzi, Jacob Kaplan, Kenneth Nepple, Aliasger K Salem, Russell W Jenkins, Yousef Zakharia and Weizhou Zhang

Communications biology, Vol.4(1), pp.122-122

01/27/2021

DOI: 10.1038/s42003-020-01625-6

PMCID: PMC7840906

PMID: 33504936

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Abstract

Clear cell renal cell carcinoma (ccRCC) is one of the most immunologically distinct tumor types due to high response rate to immunotherapies, despite low tumor mutational burden. To characterize the tumor immune microenvironment of ccRCC, we applied single-cell-RNA sequencing (SCRS) along with T-cell-receptor (TCR) sequencing to map the transcriptomic heterogeneity of 25,688 individual CD45 lymphoid and myeloid cells in matched tumor and blood from three patients with ccRCC. We also included 11,367 immune cells from four other individuals derived from the kidney and peripheral blood to facilitate the identification and assessment of ccRCC-specific differences. There is an overall increase in CD8 T-cell and macrophage populations in tumor-infiltrated immune cells compared to normal renal tissue. We further demonstrate the divergent cell transcriptional states for tumor-infiltrating CD8 T cells and identify a MKI67 + proliferative subpopulation being a potential culprit for the progression of ccRCC. Using the SCRS gene expression, we found preferential prediction of clinical outcomes and pathological diseases by subcluster assignment. With further characterization and functional validation, our findings may reveal certain subpopulations of immune cells amenable to therapeutic intervention.

Details

Title: Subtitle: Mapping the immune environment in clear cell renal carcinoma by single-cell genomics
Creators: Nicholas Borcherding - Washington University in St. Louis
Ajaykumar Vishwakarma - University of Iowa
Andrew P Voigt - University of Iowa
Andrew Bellizzi - University of Iowa Hospitals and Clinics
Jacob Kaplan - University of Iowa Hospitals and Clinics
Kenneth Nepple - University of Iowa
Aliasger K Salem - University of Iowa
Russell W Jenkins - Harvard University
Yousef Zakharia - University of Iowa
Weizhou Zhang - University of Florida
Resource Type: Journal article
Publication Details: Communications biology, Vol.4(1), pp.122-122
DOI: 10.1038/s42003-020-01625-6
PMID: 33504936
PMCID: PMC7840906
NLM abbreviation: Commun Biol
eISSN: 2399-3642
Grant note: R01 CA203834 / NCI NIH HHS R01 CA200673 / NCI NIH HHS T32 GM007337 / NIGMS NIH HHS P30 CA086862 / NCI NIH HHS R01 CA260239 / NCI NIH HHS
Language: English
Date published: 01/27/2021
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Dermatology; Hematology, Oncology, and Blood & Marrow Transplantation; The University of Iowa Institute for Vision Research; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology; Craniofacial Anomalies Research Center; Urology; Dental Research; Chemical and Biochemical Engineering; Internal Medicine
Record Identifier: 9984185177602771

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