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

• Published in: Oncotarget Vol. 8; no. 22; pp. 35656 - 35668
• Main Authors: Mego, Michal, Gao, Hui, Cohen, Evan N, Anfossi, Simone, Giordano, Antonio, Tin, Sanda, Fouad, Tamer M, De Giorgi, Ugo, Giuliano, Mario, Woodward, Wendy A, Alvarez, Ricardo H, Valero, Vicente, Ueno, Naoto T, Hortobagyi, Gabriel N, Cristofanilli, Massimo, Reuben, James M
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 30.05.2017
• Subjects: Adaptive Immunity; Adult; Aged; Cell Count; Cytokines - metabolism; Dendritic Cells - metabolism; Dendritic Cells - pathology; Female; Humans; Immunity, Innate; Inflammatory Breast Neoplasms - immunology; Inflammatory Breast Neoplasms - mortality; Inflammatory Breast Neoplasms - pathology; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Neoplastic Cells, Circulating - pathology; Prognosis; Receptors, Chemokine - metabolism; Research Paper; Survival Analysis; circulating tumors cells; inflammatory breast cancer; dendritic cells; innate immunity; adaptive immunity
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.10290

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.