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CD66b+ monocytes represent a proinflammatory myeloid subpopulation in cancer

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Abstract

Myeloid-derived suppressor cells (MDSC) populate the peripheral blood and contribute to immune regulation in cancer. However, there is limited knowledge on the myeloid cell types with proinflammatory capacities that may serve as opponents of MDSC. In the circulation of cancer patients, a monocyte subpopulation was identified with a specific immunophenotype and transcriptomic signature. They were predominantly CD14+CD33hiCD16−/+HLA-DR+/hi cells that typically expressed CD66b. In accordance with the transcriptomics data, NALP3, LOX-1 and PAI-1 levels were also significantly upregulated. The CD66b+ monocytes displayed high phagocytic activity, matrix adhesion and migration, and provided costimulation for T cell proliferation and IFN-γ secretion; thus, they did not suppress T cell responses. Irrespective of clinical stage, they were identified in various cancers. In conclusion, the CD66b+ monocytes represent a novel myeloid subpopulation which is devoid of immune regulatory influences of cancer and displays enhanced proinflammatory capacities.

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Acknowledgements

This work was partially supported by The Scientific and Technological Research Council of Turkey, (TÜBİTAK; Project No. 115S636) and Hacettepe University Scientific Research and Coordination Unit, (Grant No. TSA-2018-17239), and covered under the European Cooperation in Science and Technology (COST-EU) Action BM1404 (Mye-EUNITER) (https://www.myeeuniter.eu). COST is supported by the EU Framework Program Horizon 2020. We acknowledge the technical support by Beren Karaosmanoglu, PhD. The authors thank all patients and nurses who contributed to the study, especially Nuraydın Sahin for providing blood samples.

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  1. Digdem Yoyen-Ermis

    Present address: Department of Immunology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey

  2. Kerim Bora Yilmaz

    Present address: Department of General Surgery, Gulhane Faculty of Medicine, University of Health Sciences, Ankara, Turkey

Authors and Affiliations

  1. Department of Basic Oncology, Hacettepe University Cancer Institute, 06230, Ankara, Turkey

    Utku Horzum, Digdem Yoyen-Ermis & Gunes Esendagli

  2. Department of Medical and Surgical Research, Institute of Health Sciences, Hacettepe University, Ankara, Turkey

    Ekim Z. Taskiran, Kerim Bora Yilmaz, Erhan Hamaloglu, Derya Karakoc & Gunes Esendagli

  3. Department of Medical Genetics, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Ekim Z. Taskiran

  4. Department of General Surgery, Diskapi Yildirim Beyazit Research and Training Hospital, University of Health Sciences, Ankara, Turkey

    Kerim Bora Yilmaz

  5. Department of General Surgery, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Erhan Hamaloglu & Derya Karakoc

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Contributions

G.E. conceptualized the project and designed the experiments. U.H. and D.Y.-E. performed experiments. G.E., U.H., and D.Y.-E. interpreted data. U.H. performed bioinformatics analysis of RNA-seq data and contributed to preparation of the figures. E.Z.T performed assays related to transcriptomics. K.B.Y., E.H., and D.K. assisted with histopathological and clinical evaluation of the patients. G.E. and U.H. wrote the manuscript. All authors reviewed and approved the manuscript.

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Correspondence to Gunes Esendagli.

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Horzum, U., Yoyen-Ermis, D., Taskiran, E.Z. et al. CD66b+ monocytes represent a proinflammatory myeloid subpopulation in cancer. Cancer Immunol Immunother 70, 75–87 (2021). https://doi.org/10.1007/s00262-020-02656-y

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