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高风险三阴性早期乳腺癌患者的多重高通量免疫细胞成像:来自国际乳腺癌研究组(IBCSG)22-00 试验的分析

英文原题:Multiplexed high-throughput immune cell imaging in patients with high-risk triple negative early breast cancer: Analysis from the International Breast Cancer Study Group (IBCSG) Trial 22-00.

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Multiplexed high-throughput immune cell imaging in patients with high-risk triple negative early breast cancer: Analysis from the International Breast Cancer Study Group (IBCSG) Trial 22-00.

PubMed 2024/01/24(内容时间) Eur J Cancer Q1 · IF 7.9(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

研究概要

免疫细胞浸润的免疫空间分类似乎至关重要,可能有助于临床试验中的患者选择,并极大提高对特定疗法的应答。

研究思路结论见上方概要

三阴性乳腺癌(TNBC)是最具侵袭性的乳腺癌(BC)亚型,晚期预后差且治疗选择有限,但该亚型中的间质TIL(肿瘤浸润淋巴细胞)(sTILs)具有预测作用。

国际乳腺癌研究组(IBCSG)22-00试验是一项随机III期临床试验,旨在检验早期激素受体阴性乳腺癌患者在接受标准辅助化疗后,采用低剂量节拍口服环磷酰胺-甲氨蝶呤(CM)维持治疗的有效性。研究采用了病例-队列抽样。我们通过6色免疫荧光(IF)染色检测CD4、FOXP3、CD3、细胞角蛋白和CD8,对TNBC患者的免疫细胞浸润进行了特征分析。 结果:我们证实,高免疫CD3+ T细胞以及基质和上皮内Tregs(CD4+Foxp3+ T细胞)浸润与更好的远处无复发生存间期(DRFI)相关,尤其是在LN+患者中,且与治疗无关。更重要的是,我们发现基线时免疫细胞的空间分布至关重要,因为CM维持治疗对T细胞排斥型LN+ TNBC患者有害。

展开英文摘要原文

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer (BC) subtype, with dismal prognosis and limited option in advanced settings, yet stromal tumor infiltrating lymphocytes (sTILs) in this subtype has a predictive role.

The International Breast Cancer Study Group (IBCSG) Trial 22-00 is a randomized phase III clinical trial testing the efficacy of low-dose metronomic oral Cyclophosphamide-Methotrexate (CM) maintenance following standard adjuvant chemotherapy treatment for early-stage hormone receptor-negative breast cancer patients. A case-cohort sampling was used. We characterized immune cells infiltrates in patients with TNBC by 6 plex immunofluorescence (IF) staining for CD4, FOXP3, CD3, cytokeratine and CD8 RESULTS: We confirmed that high immune CD3 + T cells as well as stromal and intra-epithelial Tregs (CD4 + Foxp3 + T cells) infiltrates were associated with a better Distant Recurrence-Free Interval (DRFI), especially in LN+ patient, regardless of the treatment. More importantly, we showed that the spatial distribution of immune cells at baseline is crucial, as CM maintenance was detrimental for T cells excluded LN+ TNBC patients.

immune spatial classification on immune cells infiltrates seems crucial and could help patients' selection in clinical trial and greatly improve responses to specific therapies.

论文信息

作者
Rusakiewicz S、Tyekucheva S、Tissot-Renaud S、Chaba K、Imbimbo M、Benedetti F、Kammler R、Hornfeld J
第一作者单位
Department of Oncology, Lausanne University Hospital (CHUV), Lausanne, Switzerland; Center of Experimental Therapeutics, Department of Oncology, University Hospital of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland.Switzerland
通讯作者单位
European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milano, Milan, Italy. Electronic address: giuseppe.curigliano@ieo.it.Italy
期刊
European journal of cancer (Oxford, England : 1990)2024 Mar
原文标识
PubMed 38309015 · DOI 10.1016/j.ejca.2024.113535