title: Myeloid cells in circulation and tumor microenvironment of breast cancer patients.
abstract: Pathological conditions including cancers lead to accumulation of a morphological mixture of highly immunosuppressive cells termed as myeloid-derived suppressor cells (MDSC). The lack of conclusive markers to identify human MDSC, due to their heterogeneous nature and close phenotypical and functional proximity with other cell subsets, made it challenging to identify these cells. Nevertheless, expansion of MDSC has been reported in periphery and tumor microenvironment of various cancers. The majority of studies on breast cancers were performed on murine models and hence limited literature is available on the relation of MDSC accumulation with clinical settings in breast cancer patients. The aim of this study was to investigate levels and phenotypes of myeloid cells in peripheral blood (n = 23) and tumor microenvironment of primary breast cancer patients (n = 7), compared with blood from healthy donors (n = 21) and paired non-tumor normal breast tissues from the same patients (n = 7). Using multicolor flow cytometric assays, we found that breast cancer patients had significantly higher levels of tumor-infiltrating myeloid cells, which comprised of granulocytes (P = 0.022) and immature cells that lack the expression of markers for fully differentiated monocytes or granulocytes (P = 0.016). Importantly, this expansion was not reflected in the peripheral blood. The immunosuppressive potential of these cells was confirmed by expression of Arginase 1 (ARG1), which is pivotal for T-cell suppression. These findings are important for developing therapeutic modalities to target mechanisms employed by immunosuppressive cells that generate an immune-permissive environment for the progression of cancer.
authors.affiliation: College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.|Cancer Research Center, Qatar Biomedical Research Institute, College of Science and Engineering, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
authors.forename: Salman M
authors.initials: SM
authors.lastname: Toor
authors.affiliation: College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.|Cancer Research Center, Qatar Biomedical Research Institute, College of Science and Engineering, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
authors.forename: Azharuddin Sajid
authors.initials: AS
authors.lastname: Syed Khaja
authors.affiliation: Surgery Department, Tawam Hospital, Al Ain, United Arab Emirates.|Oncology Department, Al Noor Hospital, Abu Dhabi, United Arab Emirates.
authors.forename: Haytham
authors.initials: H
authors.lastname: El Salhat
authors.affiliation: Surgery Department, Tawam Hospital, Al Ain, United Arab Emirates.
authors.forename: Issam
authors.initials: I
authors.lastname: Faour
authors.affiliation: Oncology Department, Tawam Hospital, Al Ain, United Arab Emirates.
authors.forename: Jihad
authors.initials: J
authors.lastname: Kanbar
authors.affiliation: Pathology Department, Tawam Hospital, Al Ain, United Arab Emirates.
authors.forename: Asif A
authors.initials: AA
authors.lastname: Quadri
authors.affiliation: Surgery Department, Tawam Hospital, Al Ain, United Arab Emirates.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Albashir
authors.affiliation: College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. eelkord@hbku.edu.qa.|Cancer Research Center, Qatar Biomedical Research Institute, College of Science and Engineering, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar. eelkord@hbku.edu.qa.|Institute of Cancer Sciences, University of Manchester, Manchester, UK. eelkord@hbku.edu.qa.
authors.forename: Eyad
authors.identifier: http://orcid.org/0000-0002-3868-0318
authors.initials: E
authors.lastname: Elkord
mesh_terms: D000328:Adult; D000368:Aged; D001119:Arginase / Q000378:metabolism; D001940:Breast / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D019139:Tumor Escape; D059016:Tumor Microenvironment / Q000276:immunology*; D055815:Young Adult
chemical_list: C574619:ARG1 protein, human; D001119:Arginase
keywords: Breast cancer; Circulation; Myeloid cells; Myeloid-derived suppressor cells; Neutrophils; Tumor microenvironment