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A gene expression signature of TREM2hi macrophages and γδ T cells predicts immunotherapy response

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  • Donghai Xiong

    (Medical College of Wisconsin)

  • Yian Wang

    (Medical College of Wisconsin)

  • Ming You

    (Medical College of Wisconsin)

Abstract

Identifying factors underlying resistance to immune checkpoint therapy (ICT) is still challenging. Most cancer patients do not respond to ICT and the availability of the predictive biomarkers is limited. Here, we re-analyze a publicly available single-cell RNA sequencing (scRNA-seq) dataset of melanoma samples of patients subjected to ICT and identify a subset of macrophages overexpressing TREM2 and a subset of gammadelta T cells that are both overrepresented in the non-responding tumors. In addition, the percentage of a B cell subset is significantly lower in the non-responders. The presence of these immune cell subtypes is corroborated in other publicly available scRNA-seq datasets. The analyses of bulk RNA-seq datasets of the melanoma samples identify and validate a signature - ImmuneCells.Sig - enriched with the genes characteristic of the above immune cell subsets to predict response to immunotherapy. ImmuneCells.Sig could represent a valuable tool for clinical decision making in patients receiving immunotherapy.

Suggested Citation

  • Donghai Xiong & Yian Wang & Ming You, 2020. "A gene expression signature of TREM2hi macrophages and γδ T cells predicts immunotherapy response," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18546-x
    DOI: 10.1038/s41467-020-18546-x
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    Cited by:

    1. Alexander Coulton & Jun Murai & Danwen Qian & Krupa Thakkar & Claire E. Lewis & Kevin Litchfield, 2024. "Using a pan-cancer atlas to investigate tumour associated macrophages as regulators of immunotherapy response," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Kuang Du & Shiyou Wei & Zhi Wei & Dennie T. Frederick & Benchun Miao & Tabea Moll & Tian Tian & Eric Sugarman & Dmitry I. Gabrilovich & Ryan J. Sullivan & Lunxu Liu & Keith T. Flaherty & Genevieve M. , 2021. "Pathway signatures derived from on-treatment tumor specimens predict response to anti-PD1 blockade in metastatic melanoma," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. Sarah Cappuyns & Gino Philips & Vincent Vandecaveye & Bram Boeckx & Rogier Schepers & Thomas Van Brussel & Ingrid Arijs & Aurelie Mechels & Ayse Bassez & Francesca Lodi & Joris Jaekers & Halit Topal &, 2023. "PD-1- CD45RA+ effector-memory CD8 T cells and CXCL10+ macrophages are associated with response to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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