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Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages (Hematopoietic - Gene expression)

Aleksandar Obradovic, Nivedita Chowdhury, Scott M Haake, Casey Ager, Vinson Wang, Lukas Vlahos, Xinzheng V Guo, David H Aggen, W Kimryn Rathmell, Eric Jonasch, Joyce E Johnson, Marc Roth, Kathryn E Beckermann, Brian I Rini, James McKiernan, Andrea Califano, Charles G Drake

Clear cell renal carcinoma (ccRCC) is a heterogeneous disease with a variable post-surgical course. To assemble a comprehensive ccRCC tumor microenvironment (TME) atlas, we performed single-cell RNA sequencing (scRNA-seq) of hematopoietic and non-hematopoietic subpopulations from tumor and tumor-adjacent tissue of treatment-naive ccRCC resections. We leveraged the VIPER algorithm to quantitate single-cell protein activity and validated this approach by comparison to flow cytometry. The analysis identified key TME subpopulations, as well as their master regulators and candidate cell-cell interactions, revealing clinically relevant populations, undetectable by gene-expression analysis. Specifically, we uncovered a tumor-specific macrophage subpopulation characterized by upregulation of TREM2/APOE/C1Q, validated by spatially resolved, quantitative multispectral immunofluorescence. In a large clinical validation cohort, these markers were significantly enriched in tumors from patients who recurred following surgery. The study thus identifies TREM2/APOE/C1Q-positive macrophage infiltration as a potential prognostic biomarker for ccRCC recurrence, as well as a candidate therapeutic target. Keywords: kidney, renal, cancer, tumor

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Species: human
Number of cells: 102385
Number of downloads: 4
Study size: 2GB
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Immunology 
Oncology 
Kidney 
Clear cell renal carcinoma