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循环 CD8CD28 抑制性 T 细胞与接受过继性 T 细胞治疗的转移性乳腺癌患者预后较差相关:一项队列研究。

Circulating CD8CD28 suppressor T cells tied to poorer prognosis among metastatic breast cancer patients receiving adoptive T-cell therapy: A cohort study.

机构信息

Department of Medical Oncology, Beijing Key Lab for Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University Cancer Center, Beijing, China.

Department of Medical Oncology, Beijing Key Lab for Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University Cancer Center, Beijing, China; Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA; Department of Medical Oncology, Peking University Cancer Hospital, Beijing, China.

出版信息

Cytotherapy. 2018 Jan;20(1):126-133. doi: 10.1016/j.jcyt.2017.08.018. Epub 2017 Oct 4.

DOI:10.1016/j.jcyt.2017.08.018
PMID:28988693
Abstract

BACKGROUND AIMS

This study aimed to determine the prognostic value of circulating CD8CD28 T lymphocytes among breast cancer patients treated with adoptive T-lymphocyte immunotherapy after chemotherapy.

METHODS

Two hundred and thirty-two breast cancer patients underwent adoptive T-cell immunotherapy. Circulating CD8CD28 proportion was measured by flow cytometry. Median proportion of CD8CD28 was 24.2% and set as the categorical cutoff value for further analysis. The median survival was estimated by Kaplan-Meier curve, with difference detection and hazard ratio estimation by log-rank test and Cox hazard proportion regression model.

RESULTS

With adoptive T-cell therapy, patients with higher CD8CD28 levels experienced median progression-free and overall survival of 7.1 months and 26.9 months, respectively-significantly shorter than patients with lower levels (11.8 and 36.2 months). CD8CD28 proportion >24.2% demonstrated a hazard ratio (HR) of 2.06 (95% confidence interval [CI] 1.31-3.12) for progression and an HR of 1.97 (95% CI 1.06-3.67) for death. Among patients who had received previous first-line chemotherapy, CD8CD28 proportion >24.2% demonstrated an HR of 2.66 (95% CI 1.45-4.88) for progression. Among patients exposed to previous second-line or higher chemotherapy, CD8CD28 proportion >24.2% demonstrated a 486% higher risk for death (HR = 5.86, 95% CI 1.77-19.39). A 1% increase in suppressive T cells was associated with a 5% increased risk of death.

DISCUSSION

Elevated peripheral blood CD8CD28 was associated with poorer prognosis for metastatic breast cancer, especially for higher risk of progression among patients with first-line chemotherapy and higher risk of death among patients with more than second-line chemotherapy.

摘要

背景目的

本研究旨在确定化疗后接受过继性 T 淋巴细胞免疫疗法治疗的乳腺癌患者循环 CD8CD28 T 淋巴细胞的预后价值。

方法

232 例乳腺癌患者接受过继性 T 细胞免疫治疗。通过流式细胞术测量循环 CD8CD28 比例。CD8CD28 的中位数比例为 24.2%,并设定为进一步分析的分类截断值。通过 Kaplan-Meier 曲线估计中位生存期,对数秩检验和 Cox 风险比例回归模型检测差异和风险比估计。

结果

接受过继性 T 细胞治疗的患者,CD8CD28 水平较高者的中位无进展生存期和总生存期分别为 7.1 个月和 26.9 个月,明显短于水平较低者(11.8 个月和 36.2 个月)。CD8CD28 比例>24.2%的患者进展的风险比(HR)为 2.06(95%置信区间[CI] 1.31-3.12),死亡的 HR 为 1.97(95% CI 1.06-3.67)。在接受过一线化疗的患者中,CD8CD28 比例>24.2%的患者进展的 HR 为 2.66(95% CI 1.45-4.88)。在接受过二线或更高线化疗的患者中,CD8CD28 比例>24.2%的患者死亡风险增加 486%(HR=5.86,95% CI 1.77-19.39)。抑制性 T 细胞增加 1%,死亡风险增加 5%。

讨论

外周血 CD8CD28 升高与转移性乳腺癌的预后较差相关,尤其是一线化疗患者的进展风险较高,二线以上化疗患者的死亡风险较高。

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