Circulating Tumor Cells (CTC) Are Associated with Defects in Adaptive Immunity in Patients with Inflammatory Breast Cancer.
Circulating Tumor Cells (CTC) Are Associated with Defects in Adaptive Immunity in Patients with Inflammatory Breast Cancer.
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DOI：
10.7150/jca.13098
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发表时间：
2016
影响因子：
3.9
通讯作者：
Reuben JM
中科院分区：
文献类型：
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作者：
Mego M;Gao H;Cohen EN;Anfossi S;Giordano A;Sanda T;Fouad TM;De Giorgi U;Giuliano M;Woodward WA;Alvarez RH;Valero V;Ueno NT;Hortobagyi GN;Cristofanilli M;Reuben JM
背景：循环肿瘤细胞（CTC）在肿瘤扩散中起着至关重要的作用，并且在原发性和转移性乳腺癌中具有预后意义。外周血（PB）免疫细胞有助于CTC存活的不利微环境。本研究旨在将CTC与炎性乳腺癌（IBC）患者的PB T细胞免疫表型和功能相关联。方法：本研究包括65例在MD安德森癌症中心接受治疗的IBC患者。在开始新的化疗线之前从患者获得PB，用于通过CellSearch®进行CTC计数，并通过流式细胞术进行T细胞表型和功能;结果与CTC和临床结果相关。结果：61.5%和32.3%的患者至少检测到1个CTC（≥1个）或≥5个CTC。CTC计数与总淋巴细胞无关;然而，与无CTC或<5个CTC的患者相比，具有≥1个CTC或≥ 5个CTC的患者的CD 3+和CD 4 + T细胞百分比（%）分别较低。与无CTC的患者相比，具有≥1个CTC的患者合成TNF-α和IFN-γ的T细胞受体（TCR）激活的CD 8 + T细胞百分比较低，调节性T淋巴细胞百分比较高。在多变量分析中，肿瘤分级和%CD 3 + T细胞与≥1个CTC相关，而≥5个CTC与肿瘤分级、分期、%CD 3+和%CD 4 + T细胞以及合成IL-17的%TCR活化CD 8 T细胞相关。结论：PB中存在CTC的IBC患者的适应性免疫异常可能会影响肿瘤细胞播散和转移级联反应的启动。
Background: 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). Methods: 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. Results: 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. Conclusions: IBC patients with CTCs in PB had abnormalities in adaptive immunity that could potentially impact tumor cell dissemination and initiation of the metastatic cascade.