Mego M, Gao H, Cohen E N, Anfossi S, Giordano A, Sanda T, Fouad T M, De Giorgi U, Giuliano M, Woodward W A, Alvarez R H, Valero V, Ueno N T, Hortobagyi G N, Cristofanilli M, Reuben J M
1. Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;; 5. Currently at 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia;
1. Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
J Cancer. 2016 Jun 3;7(9):1095-104. doi: 10.7150/jca.13098. eCollection 2016.
Circulating tumor cells (CTCs) play a crucial role in tumor dissemination and are prognostic in primary and metastatic breast cancer. Peripheral blood (PB) immune cells contribute to an unfavorable microenvironment for CTC survival. This study aimed to correlate CTCs with the PB T-cell immunophenotypes and functions of patients with inflammatory breast cancer (IBC).
This study included 65 IBC patients treated at the MD Anderson Cancer Center. PB was obtained from patients prior to starting a new line of chemotherapy for CTCs enumeration by CellSearch(®), and T cell phenotype and function by flow cytometry; the results were correlated with CTCs and clinical outcome.
At least 1 CTC (≥1) or ≥5 CTCs was detected in 61.5% or 32.3% of patients, respectively. CTC count did not correlate with total lymphocytes; however, patients with ≥1 CTC or ≥5 CTCs had lower percentages (%) of CD3+ and CD4+ T cells compared with patients with no CTCs or <5 CTCs, respectively. Patients with ≥1 CTC had a lower percentage of T-cell receptor (TCR)-activated CD8+ T cells synthesizing TNF-α and IFN-γ and a higher percentage of T-regulatory lymphocytes compared to patients without CTCs. In multivariate analysis, tumor grade and % CD3+ T-cells were associated with ≥1 CTC, whereas ≥5 CTC was associated with tumor grade, stage, % CD3+ and % CD4+ T cells, and % TCR-activated CD8 T-cells synthesizing IL-17.
IBC patients with CTCs in PB had abnormalities in adaptive immunity that could potentially impact tumor cell dissemination and initiation of the metastatic cascade.
循环肿瘤细胞（CTC）在肿瘤播散中起关键作用，对原发性和转移性乳腺癌具有预后价值。外周血（PB）免疫细胞为CTC存活营造了不利的微环境。本研究旨在关联炎性乳腺癌（IBC）患者的CTC与PB T细胞免疫表型及功能。
本研究纳入了在MD安德森癌症中心接受治疗的65例IBC患者。在开始新一轮化疗前采集患者的PB，通过CellSearch®计数CTC，并采用流式细胞术检测T细胞表型和功能；将结果与CTC及临床结局相关联。
分别在61.5%或32.3%的患者中检测到至少1个CTC（≥1）或≥5个CTC。CTC计数与总淋巴细胞数无相关性；然而，与无CTC或＜5个CTC的患者相比，≥1个CTC或≥5个CTC的患者CD3⁺和CD4⁺T细胞百分比更低。与无CTC的患者相比，≥1个CTC的患者合成肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的T细胞受体（TCR）激活的CD8⁺T细胞百分比更低，而调节性T淋巴细胞百分比更高。多因素分析显示，肿瘤分级和CD3⁺T细胞百分比与≥1个CTC相关，而≥5个CTC与肿瘤分级、分期、CD3⁺和CD4⁺T细胞百分比以及合成白细胞介素-17（IL-17）的TCR激活的CD8 T细胞百分比相关。
PB中存在CTC的IBC患者适应性免疫存在异常，这可能会影响肿瘤细胞播散及转移级联反应的启动。
