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
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.
Oncotarget. 2017 May 30;8(22):35656-35668. 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.
循环肿瘤细胞（CTCs）参与肿瘤播散，是原发性和转移性乳腺癌患者的独立预后因素。树突状细胞（DCs）是最有效的抗原呈递细胞，由浆细胞样（pDC）和髓样（mDC）来源的DC亚群组成。本研究旨在将CTCs计数与炎性乳腺癌（IBC）患者外周血DC免疫表型及功能相关联。本研究纳入了65例IBC患者。在开始新的化疗方案之前采集患者外周血（PB），通过CellSearch®计数CTCs，并通过流式细胞术检测DC表型和功能；然后将DC的特征与CTCs计数及临床结局相关联。21例（32.3%）CTCs≥5的患者总生存期（OS）明显低于CTCs＜5的患者（p=0.045）。此外，CTCs≥5的患者中，通过Toll样受体（TLR）激活前后能够产生肿瘤坏死因子-α（TNF-α）的mDC百分比更低，TLR激活后产生白细胞介素-12（IL-12）的mDC百分比也更低。CTCs计数分别与TLR激活的mDC和pDC上激活受体（CCR7）及共刺激受体（CD86）的表达呈正相关。此外，能够产生更高水平TNF-α的高百分比mDC的存在与较差的OS独立相关（p = 0.0006）。产生TNF-α的mDC百分比增加可能诱导促炎环境，这可能在决定IBC患者不良临床结局中起作用，并可为CTCs增加进一步的预后价值。
