title: Systemic Monocytic-MDSCs Are Generated from Monocytes and Correlate with Disease Progression in Breast Cancer Patients.
abstract: Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, which increase in cancer patients. The molecular mechanism behind their generation and function is unclear. Whereas granulocytic-MDSCs correlate with poor overall survival in breast cancer, the presence and relevance of monocytic-MDSCs (Mo-MDSCs) is unknown. Here we report for the first time an enrichment of functional blood Mo-MDSCs in breast cancer patients before they acquire a typical Mo-MDSC surface phenotype. A clear population of Mo-MDSCs with the typical cell surface phenotype (CD14(+)HLA-DR(low/-)CD86(low/-)CD80(low/-)CD163(low/-)) increased significantly first during disease progression and correlated to metastasis to lymph nodes and visceral organs. Furthermore, monocytes, comprising the Mo-MDSC population, from patients with metastatic breast cancer resemble the reprogrammed immunosuppressive monocytes in patients with severe infections, both by their surface and functional phenotype but also at their molecular gene expression profile. Our data suggest that monitoring the Mo-MDSC levels in breast cancer patients may represent a novel and simple biomarker for assessing disease progression.
authors.affiliation: Center for Molecular Pathology, Jan Waldenströms gata 59, Skåne University Hospital (SUS), Lund University (LU), 20502 Malmö, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bergenfelz
authors.affiliation: Translational Cancer Research, LU, Medicon Village 22381 Lund, Sweden.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Larsson
authors.affiliation: Translational Cancer Research, LU, Medicon Village 22381 Lund, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: von Stedingk
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences Lund, LU, 22185 Lund, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Gruvberger-Saal
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences Lund, LU, 22185 Lund, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Aaltonen
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences Lund, LU, 22185 Lund, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Jansson
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences Lund, LU, 22185 Lund, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Jernström
authors.affiliation: Department of Infectious Diseases, SUS, LU, 20502 Malmö, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Janols
authors.affiliation: Department of Infectious Diseases, SUS, LU, 20502 Malmö, Sweden.
authors.forename: Marlene
authors.initials: M
authors.lastname: Wullt
authors.affiliation: Medical Microbiology, Jan Waldenströms gata 59, SUS, LU, 20502 Malmö, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Bredberg
authors.affiliation: Division of Surgery, Department of Clinical Sciences LU, 22185 Lund, Sweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rydén
authors.affiliation: Center for Molecular Pathology, Jan Waldenströms gata 59, Skåne University Hospital (SUS), Lund University (LU), 20502 Malmö, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Leandersson
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D002452:Cell Count; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology*; D022423:Myeloid Cells / Q000473:pathology*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D011971:Receptors, Immunologic / Q000378:metabolism; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D011971:Receptors, Immunologic