Coupled scRNA-Seq and Intracellular Protein Activity Reveal an Immunosuppressive Role of TREM2 in Cancer
Open accessAbstract
Cell function and activity are regulated through integration of signaling, epigenetic, transcriptional, and metabolic pathways. Here, we introduce INs-seq, an integrated technology for massively parallel recording of single-cell RNA sequencing (scRNA-seq) and intracellular protein activity. We demonstrate the broad utility of INs-seq for discovering new immune subsets by profiling different intracellular signatures of immune signaling, transcription factor combinations, and metabolic activity. Comprehensive mapping of Arginase 1-expressing cells within tumor models, a metabolic immune signature of suppressive activity, discovers novel Arg1+ Trem2+ regulatory myeloid (Mreg) cells and identifies markers, metabolic activity, and pathways associated with these cells. Genetic ablation of Trem2 in mice inhibits accumulation of intra-tumoral Mreg cells, leading to a marked decrease in dysfunctional CD8+ T cells and reduced tumor growth. This study establishes INs-seq as a broadly applicable technology for elucidating integrated transcriptional and intra-cellular maps and identifies the molecular signature of myeloid suppressive cells in tumors.
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TREM2+ macrophages play a highly immunosuppressive role in the tumor microenvironment.
“Others have shown that TREM2+ macrophages play a highly immunosuppressive role in the tumor microenvironment79”
From Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy (2023) · cites this paper as [79]
Technologies profiling both intracellular and cell-surface proteins can better elucidate signalling pathways required for single-cell function.
“Technologies that can profile both intracellular and cell-surface proteins can better elucidate the signalling pathways that required for the function of a single cell75,76.”
From The technological landscape and applications of single-cell multi-omics (2023) · cites this paper as [76]
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Single-cell profiling of proteins and chromatin accessibility using PHAGE-ATAC
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TREM2: Keeping Pace With Immune Checkpoint Inhibitors in Cancer Immunotherapy
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Determinants, mechanisms, and functional outcomes of myeloid cell diversity in cancer
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- Authors
- Katzenelenbogen, Y., Sheban, F., Yalin, A., Yofe, I., Svetlichnyy, D., Jaitin, D. A., Bornstein, C., Moshe, A., Keren-Shaul, H., Cohen, M., Wang, S.-Y., Li, B., David, E., Salame, T.-M., Weiner, A., & Amit, I.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Weiner, Assaf
- Amit, Ido
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 182
- Issue
- 4
- Pages
- 872-885.e19
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W3048711673
- Cited by
- 498
- References
- 63
- Citations by year
- 2026: 58 · 2025: 82 · 2024: 82 · 2023: 100 · 2022: 100 · 2021: 61 · 2020: 14
- FWCI
- 22.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- TREM2, arginase-1, tumor immunosuppression, single-cell transcriptomics, CD8+ T cell dysfunction, tumor microenvironment
- MeSH terms
- Animals, Arginase, Dendritic Cells, Female, Gene Expression Regulation, Humans, Leukocytes, Mononuclear, Lipopolysaccharides, Membrane Glycoproteins, Mice, Inbred C57BL, Neoplasms, Receptors, Immunologic, Transcription Factors, Tumor Necrosis Factor-alpha, Sequence Analysis, RNA, CD8-Positive T-Lymphocytes, RNA, Small Cytoplasmic, p38 Mitogen-Activated Protein Kinases, Mice, Single-Cell Analysis, Tumor Microenvironment
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