4.7 Article

CD66b+monocytes represent a proinflammatory myeloid subpopulation in cancer

Journal

CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 70, Issue 1, Pages 75-87

Publisher

SPRINGER
DOI: 10.1007/s00262-020-02656-y

Keywords

Myeloid-derived suppressor cells (MDSC); Monocyte; PMN-MDSC; Transcriptomics; Monocyte subtypes; Neutrophil

Funding

  1. Scientific and Technological Research Council of Turkey, (TUBITAK) [115S636]
  2. Hacettepe University Scientific Research and Coordination Unit [TSA-2018-17239]
  3. European Cooperation in Science and Technology (COSTEU) Action [BM1404]
  4. EU Framework Program Horizon 2020

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In cancer patients, a specific subpopulation of monocytes expressing CD66b was identified in the circulation. These monocytes displayed high phagocytic activity, matrix adhesion, and migration, and provided costimulation for T cell proliferation and IFN-gamma secretion without suppressing T cell responses. They represent a novel myeloid subpopulation which lacks immune regulatory influences and shows enhanced proinflammatory capacities.
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(+)CD33(hi)CD16(-/+)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-gamma 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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