PMID- 27374101 OWN - NLM STAT- MEDLINE DCOM- 20180326 LR - 20220410 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 22 DP - 2017 May 30 TI - Circulating tumor cells (CTCs) are associated with abnormalities in peripheral blood dendritic cells in patients with inflammatory breast cancer. PG - 35656-35668 LID - 10.18632/oncotarget.10290 [doi] AB - 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(R) 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-alpha 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-alpha was independently associated with inferior OS (p = 0.0006). An increase in the percentage of mDC producing TNF-alpha 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. FAU - Mego, Michal AU - Mego M AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Currently at Department of Medical Oncology, Comenius University, School of Medicine, National Cancer Institute, Bratislava, Slovakia. FAU - Gao, Hui AU - Gao H AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Cohen, Evan N AU - Cohen EN AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Anfossi, Simone AU - Anfossi S AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Giordano, Antonio AU - Giordano A AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Currently at Department of Medicine at Medical University of South Carolina, Charleston, SC, USA. FAU - Tin, Sanda AU - Tin S AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Fouad, Tamer M AU - Fouad TM AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Currently at Department of Medical Oncology, The National Cancer Institute, Cairo University, Cairo, Egypt. FAU - De Giorgi, Ugo AU - De Giorgi U AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Currently at Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) - IRCCS, Meldola (FC), Italy. FAU - Giuliano, Mario AU - Giuliano M AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Currently at Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy. FAU - Woodward, Wendy A AU - Woodward WA AD - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Department of MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Alvarez, Ricardo H AU - Alvarez RH AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Department of MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Valero, Vicente AU - Valero V AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Department of MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Ueno, Naoto T AU - Ueno NT AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Department of MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Hortobagyi, Gabriel N AU - Hortobagyi GN AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Cristofanilli, Massimo AU - Cristofanilli M AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Currently at Division of Hematology-Oncology at Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. FAU - Reuben, James M AU - Reuben JM AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Department of MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. LA - eng GR - R01 CA138239/CA/NCI NIH HHS/United States PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Cytokines) RN - 0 (Receptors, Chemokine) SB - IM MH - Adaptive Immunity MH - Adult MH - Aged MH - Cell Count MH - Cytokines/metabolism MH - Dendritic Cells/*metabolism/pathology MH - Female MH - Humans MH - Immunity, Innate MH - Inflammatory Breast Neoplasms/*immunology/mortality/*pathology MH - Middle Aged MH - Neoplasm Metastasis MH - Neoplasm Staging MH - Neoplastic Cells, Circulating/*pathology MH - Prognosis MH - Receptors, Chemokine/metabolism MH - Survival Analysis PMC - PMC5482606 OTO - NOTNLM OT - adaptive immunity OT - circulating tumors cells OT - dendritic cells OT - inflammatory breast cancer OT - innate immunity COIS- CONFLICTS OF INTEREST The authors declare no competing financial and non-financial interests in relation to the work described in the manuscript. EDAT- 2016/07/05 06:00 MHDA- 2018/03/27 06:00 PMCR- 2017/05/30 CRDT- 2016/07/05 06:00 PHST- 2016/03/29 00:00 [received] PHST- 2016/05/13 00:00 [accepted] PHST- 2016/07/05 06:00 [pubmed] PHST- 2018/03/27 06:00 [medline] PHST- 2016/07/05 06:00 [entrez] PHST- 2017/05/30 00:00 [pmc-release] AID - 10290 [pii] AID - 10.18632/oncotarget.10290 [doi] PST - ppublish SO - Oncotarget. 2017 May 30;8(22):35656-35668. doi: 10.18632/oncotarget.10290.