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

Abstract

// Michal Mego 1, 5 , Hui Gao 1 , Evan N. Cohen 1 , Simone Anfossi 1 , Antonio Giordano 1, 10 , Sanda Tin 1 , Tamer M. Fouad 2, 6 , Ugo De Giorgi 1, 7 , Mario Giuliano 1, 8 , Wendy A. Woodward 3, 4 , Ricardo H. Alvarez 2, 4 , Vicente Valero 2, 4 , Naoto T. Ueno 2, 4 , Gabriel N. Hortobagyi 2 , Massimo Cristofanilli 2, 9 and James M. Reuben 1, 4 1 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 3 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4 Department of MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 5 Currently at Department of Medical Oncology, Comenius University, School of Medicine, National Cancer Institute, Bratislava, Slovakia 6 Currently at Department of Medical Oncology, The National Cancer Institute, Cairo University, Cairo, Egypt 7 Currently at Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) – IRCCS, Meldola (FC), Italy 8 Currently at Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy 9 Currently at Division of Hematology-Oncology at Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL, USA 10 Currently at Department of Medicine at Medical University of South Carolina, Charleston, SC, USA Correspondence to: James M. Reuben, email: jreuben@mdanderson.org 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 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.