Dissecting intratumoral myeloid cell plasticity by single cell RNA-seq
Open accessAbstract
Tumor‐infiltrating myeloid cells are the most abundant leukocyte population within tumors. Molecular cues from the tumor microenvironment promote the differentiation of immature myeloid cells toward an immunosuppressive phenotype. However, the in situ dynamics of the transcriptional reprogramming underlying this process are poorly understood. Therefore, we applied single cell RNA‐seq (scRNA‐seq) to computationally investigate the cellular composition and transcriptional dynamics of tumor and adjacent normal tissues from 4 early‐stage non‐small cell lung cancer (NSCLC) patients. Our scRNA‐seq analyses identified 11 485 cells that varied in identity and gene expression traits between normal and tumor tissues. Among these, myeloid cell populations exhibited the most diverse changes between tumor and normal tissues, consistent with tumor‐mediated reprogramming. Through trajectory analysis, we identified a differentiation path from CD14+ monocytes to M2 macrophages (monocyte‐to‐M2). This differentiation path was reproducible across patients, accompanied by increased expression of genes (eg, MRC1 / CD206 , MSR1 / CD204 , PPARG , TREM2 ) with significantly enriched functions (Oxidative phosphorylation and P53 pathway) and decreased expression of genes (eg, CXCL2 , IL1B ) with significantly enriched functions ( TNF‐α signaling via NF‐κB and inflammatory response). Our analysis further identified a co‐regulatory network implicating upstream transcription factors ( JUN , NFKBIA ) in monocyte‐to‐M2 differentiation, and activated ligand‐receptor interactions (eg, SFTPA1 ‐ TLR2 , ICAM1 ‐ ITGAM ) suggesting intratumoral mechanisms whereby epithelial cells stimulate monocyte‐to‐M2 differentiation. Overall, our study identified the prevalent monocyte‐to‐M2 differentiation in NSCLC, accompanied by an intricate transcriptional reprogramming mediated by specific transcriptional activators and intercellular crosstalk involving ligand‐receptor interactions.
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TREM2+ macrophages have been reported in tumors.
“TREM2+ macrophages have also been reported in tumors (Lavin et al., 2017; Song et al., 2019), but the impact of TREM2 in tumor immune responses has not been addressed.”
From TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy (2020) · cites this paper as Song et al., 2019
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Evolution and Targeting of Myeloid Suppressor Cells in Cancer: A Translational Perspective
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TREM2 knockdown improves the therapeutic effect of PD-1 blockade in hepatocellular carcinoma
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Decoding Single-cell Landscape and Intercellular Crosstalk in the Transplanted Liver
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An Agentic AI Framework for Ingestion and Standardization of Single-Cell RNA-seq Data Analysis
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IFN-α/β/IFN-γ/IL-15 pathways identify GBP1-expressing tumors with an immune-responsive phenotype
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The Presence and Potential Role of ALDH1A2 in the Glioblastoma Microenvironment
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- Authors
- Song, Q., Hawkins, G. A., Wudel, L., Chou, P., Forbes, E., Pullikuth, A. K., Liu, L., Jin, G., Craddock, L., Topaloglu, U., Kucera, G., O’Neill, S., Levine, E. A., Sun, P., Watabe, K., Lu, Y., Alexander‐Miller, M. A., Pasche, B., Miller, L. D., & Zhang, W.
- Affiliations
- Atrium Health Wake Forest Baptist (US)
- Wake Forest University Health Sciences (US)
- Center for Cancer Genomics and Precision Oncology Wake Forest Baptist Comprehensive Cancer Center, Wake Forest Baptist Medical Center Winston Salem North Carolina
- Corresponding author
- Miller, Lance D.
- Zhang, Wei
- ORCID
- Venue
- Cancer Medicine
- Publisher
- Wiley
- Published
- 2019-04-29
- Volume
- 8
- Issue
- 6
- Pages
- 3072-3085
- ISSN
- 2045-7634 (ISSN-L)
- PMC
- PMC6558497
- OpenAlex
- W2943598479
- Cited by
- 168
- References
- 54
- Citations by year
- 2026: 12 · 2025: 27 · 2024: 32 · 2023: 17 · 2022: 35 · 2021: 23 · 2020: 16 · 2019: 6
- FWCI
- 7.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Comprehensive Cancer Center, City of Hope
- Wake Forest University (P30CA012197)
- National Foundation for Cancer Research
- American Association for Cancer Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- tumor-infiltrating myeloid cells, non-small cell lung cancer, tumor microenvironment, transcriptional reprogramming, M2 macrophages, CD14+ monocytes, transcriptional regulatory networks, NF-κB signaling, c-Jun, NFKBIA, ligand-receptor interactions, immunosuppression
- MeSH terms
- Cell Plasticity, RNA-Seq, Humans, Signal Transduction, Myeloid Cells, Tumor Microenvironment
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