基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The impact of immune microenvironment on local control of ductal carcinoma in situ receiving breast conservative therapy.
The impact of immune microenvironment on local control of ductal carcinoma in situ receiving breast conservative therapy.
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我们的研究强调了总体免疫细胞亚型评估为全面评价 DCIS 患者的 IME 提供了一种工具。由生物标志物和综合 IME 特征组成的列线图显示出对 IBTR 风险进行分层以及预测 WBI 获益的潜力。
本研究旨在明确肿瘤免疫微环境(IME)在导管原位癌(DCIS)中预测全乳放疗(WBI)获益的作用。
在接受了保乳手术(BCS)的DCIS队列的肿瘤组织中,确定了TIL(肿瘤浸润淋巴细胞)(TILs)、肿瘤相关巨噬细胞(TAMs)和三级淋巴结构(TLSs)的不同亚型。
共纳入165例患者,其中113例接受了WBI。中位随访73.7个月后,发生15例同侧乳腺肿瘤复发(IBTR)事件。9例IBTR发生在原象限之外(其他部位失败事件,EFE)。经过LASSO和多因素Cox回归分析,ER阴性状态、高CD4+/CD8+比值、密集CD68+ TAMs、稀疏CD8+ T细胞以及伴有滤泡树突状细胞的密集TLSs(F-TLSs)仍是IBTR的独立危险因素(均p < 0.05),据此构建列线图。列线图的评分被定义为免疫微环境评分(IMS),将所有患者分为低、中、高风险组。这三个风险亚组之间IBTR存在显著差异(5年率:0.0% vs. 11.4% vs. 72.2%,p < 0.01)。对于整个队列,WBI的获益仅见于中风险亚组(IBTR的5年率:7.0% vs. 22.0%,p = 0.04;EFE:2.3% vs. 16.4%,p = 0.01),而在低风险和高风险组中未见获益。
This study aims to identify the role of tumor immune microenvironment (IME) in ductal carcinoma in situ (DCIS) in predicting benefit of whole breast irradiation (WBI).
Different subtypes of tumor infiltrating lymphocytes (TILs), tumor associated macrophages (TAMs) and tertiary lymphoid structures (TLSs) were determined in tumor tissues of DCIS cohort who received breast-conserving surgery (BCS).
In total, 165 patients were enrolled with 113 received WBI. After a median follow-up of 73.7 months, 15 ipsilateral breast tumor recurrence (IBTR) events occurred. Nine IBTRs occurred outside of the original quadrant (elsewhere failure event, EFE). After LASSO and multivariate Cox regression analyses, the ER negative status, high ratios of CD4 + /CD8 + , dense CD68 + TAMs, sparse CD8 + T cell and dense TLSs with follicular dendritic cells (F-TLSs) remained independent risk factors of IBTR (all p < 0.05) to develop a nomogram. Points of nomogram were defined as immune microenvironment score (IMS) which divided all patients into low-, intermediate- and high-risk groups. Significant differences in IBTR existed among these three risk subgroups (5y-rate: 0.0% vs. 11.4% vs. 72.2%, p < 0.01). For the whole cohort, the benefit of WBI was found only in the intermediate-risk subgroup (5y-rate of IBTR: 7.0% vs. 22.0%, p = 0.04; EFE: 2.3% vs. 16.4%, p = 0.01) while not in the low- and high-risk group.
Our study highlighted the assessment of overall immune cells subtypes provided a tool for comprehensive evaluation of IME in DCIS patients. The nomogram composed of biomarker and integrated IME characteristics showed the potential to stratify the risk of IBTR and predicting the benefit from WBI.
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