title: Circulating tumor cells (CTCs) are associated with abnormalities in peripheral blood dendritic cells in patients with inflammatory breast cancer.
abstract: CTCs are involved in tumor dissemination and are an independent prognostic factor in primary and metastatic breast cancer patients. Dendritic cells (DCs) are the most efficient antigen presenting cells and are comprised of plasmacytoid-(pDC) and myeloid-(mDC) derived DC subsets. This study aimed to correlate CTC counts with the peripheral blood DC immunophenotypes and functions of inflammatory breast cancer (IBC) patients. This study included 65 IBC patients. Peripheral blood (PB) was obtained from patients prior to starting a new line of chemotherapy for CTCs enumeration by CellSearch® and DC phenotype and function by flow cytometry; the characteristics of DCs were then correlated with CTC counts and clinical outcome. Twenty-one (32.3%) patients with CTCs ≥5 had a significantly inferior overall survival (OS) compared to patients with <5 CTCs (p=0.045). In addition, patients with ≥5 CTCs had a lower percentage of mDCs capable of producing TNF-α before or after activation through the toll-like receptor (TLR), as well as a lower percentage of mDCs producing IL-12 after TLR-activation. There was a positive correlation between CTCs counts and expression of the activation (CCR7) and costimulatory (CD86) receptors on TLR-activated mDCs and pDCs, respectively. Moreover, presence of high percentage of mDC capable to produce increased levels of TNF-α was independently associated with inferior OS (p = 0.0006). An increase in the percentage of mDC producing TNF-α might induce a pro-inflammatory environment that could play a role in determining the poor clinical outcome in IBC patients and could add further prognostic value to CTCs.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Currently at Department of Medical Oncology, Comenius University, School of Medicine, National Cancer Institute, Bratislava, Slovakia.
authors.forename: Michal
authors.initials: M
authors.lastname: Mego
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Evan N
authors.initials: EN
authors.lastname: Cohen
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Anfossi
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Currently at Department of Medicine at Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sanda
authors.initials: S
authors.lastname: Tin
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Currently at Department of Medical Oncology, The National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Tamer M
authors.initials: TM
authors.lastname: Fouad
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Currently at Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) - IRCCS, Meldola (FC), Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: De Giorgi
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Currently at Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Giuliano
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Woodward
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ricardo H
authors.initials: RH
authors.lastname: Alvarez
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Currently at Division of Hematology-Oncology at Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Reuben
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000368:Aged; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D058922:Inflammatory Breast Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D019707:Receptors, Chemokine / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D016207:Cytokines; D019707:Receptors, Chemokine
keywords: adaptive immunity; circulating tumors cells; dendritic cells; inflammatory breast cancer; innate immunity