Research Papers:

Circulating tumor cells (CTCs) are associated with abnormalities in peripheral blood dendritic cells in patients with inflammatory breast cancer

Michal Mego _, Hui Gao, Evan N. Cohen, Simone Anfossi, Antonio Giordano, Sanda Tin, Tamer M. Fouad, Ugo De Giorgi, Mario Giuliano, Wendy A. Woodward, Ricardo H. Alvarez, Vicente Valero, Naoto T. Ueno, Gabriel N. Hortobagyi, Massimo Cristofanilli and James M. Reuben

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Oncotarget. 2017; 8:35656-35668. https://doi.org/10.18632/oncotarget.10290

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Michal Mego1,5, Hui Gao1, Evan N. Cohen1, Simone Anfossi1, Antonio Giordano1,10, Sanda Tin1, Tamer M. Fouad2,6, Ugo De Giorgi1,7, Mario Giuliano1,8, Wendy A. Woodward3,4, Ricardo H. Alvarez2,4, Vicente Valero2,4, Naoto T. Ueno2,4, Gabriel N. Hortobagyi2, Massimo Cristofanilli2,9 and James M. Reuben1,4

1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

3Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

4Department of MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

5Currently at Department of Medical Oncology, Comenius University, School of Medicine, National Cancer Institute, Bratislava, Slovakia

6Currently at Department of Medical Oncology, The National Cancer Institute, Cairo University, Cairo, Egypt

7Currently at Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) – IRCCS, Meldola (FC), Italy

8Currently at Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy

9Currently at Division of Hematology-Oncology at Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

10Currently at Department of Medicine at Medical University of South Carolina, Charleston, SC, USA

Correspondence to:

James M. Reuben, email: [email protected]

Keywords: circulating tumors cells, innate immunity, adaptive immunity, dendritic cells, inflammatory breast cancer

Received: March 29, 2016     Accepted: May 13, 2016     Published: June 25, 2016


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.

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