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
为早期三阴性乳腺癌定制升级辅助治疗：CBCSG010 临床试验生物标志物分析
英文原题：Tailoring Escalation Adjuvant Therapy for Early-Stage Triple-Negative Breast Cancer in the CBCSG010 Clinical Trial Biomarker Analysis.
查看英文原题
Tailoring Escalation Adjuvant Therapy for Early-Stage Triple-Negative Breast Cancer in the CBCSG010 Clinical Trial Biomarker Analysis.
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研究概要
我们的研究表明，免疫热型 TNBC 患者更可能从辅助卡培他滨治疗中获益，并且免疫治疗联合化疗有望在免疫热型患者中更为有效。
研究思路结论见上方概要
背景
三阴性乳腺癌（TNBC）是一种高度异质性的疾病。CBCSG010试验是一项前瞻性、多中心的III期临床试验，证实加用辅助卡培他滨可使TNBC患者的5年无病生存期（DFS）率显著提高5.9%。在本研究中，我们试图确定从辅助治疗中获益的特定人群。
方法
在这项回顾性探索性分析中，我们对CBCSG010临床试验中TNBC患者的肿瘤组织进行了RNA测序。我们进行了单样本基因集富集分析算法和生存分析，以表征TNBC微环境的固有分子特征，并评估免疫相关基因表达水平或免疫细胞计数与卡培他滨治疗疗效之间的关联。此外，我们对2个标志物PD-L1和CD8进行了免疫组化染色，并对福尔马林固定、石蜡包埋的标本进行了间质TIL（肿瘤浸润淋巴细胞）（sTILs）的苏木精-伊红染色，以验证生物信息学分析的结果。
结果
我们发现，免疫浸润高的TNBC患者接受卡培他滨治疗后更可能获得更好的预后。我们使用PD-L1联合阳性评分（CPS）≥25、sTILs阳性≥10%以及CD8阳性细胞≥10%作为cutoff值来定义“免疫热”患者。在免疫热患者中，Kaplan-Meier曲线显示，卡培他滨组和对照组的5年DFS率分别为96.9%和79.4%（风险比，0.13；95% CI，0.03-0.52；P=.049，支持卡培他滨）。在卡培他滨组中，免疫热患者的5年DFS率高于免疫冷患者（96.9% vs 76.4%；风险比，0.11；95% CI，0.04-0.29；P=.028）。
展开英文摘要原文
BACKGROUND
Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. The CBCSG010 trial is a prospective and multicenter phase III clinical trial confirming that adding adjuvant capecitabine significantly improved the 5-year disease-free survival (DFS) rate in patients with TNBC by 5.9%. In this study, we attempted to identify the specific population that benefited from adjuvant therapy.
METHODS
In this retrospective exploratory analysis, we performed RNA sequencing of tumor tissues from patients with TNBC in the CBCSG010 clinical trial. A single-sample gene set enrichment analysis algorithm and survival analysis were performed to characterize the intrinsic molecular features of the TNBC microenvironment and assess the associations between immune-related gene expression levels or immune cell counts with capecitabine treatment efficacy. Additionally, we performed immunohistochemical staining of 2 markers, PD-L1 and CD8, and hematoxylin-eosin staining of stromal tumor-infiltrating lymphocytes (sTILs) on formalin-fixed, paraffin-embedded specimens to validate findings from bioinformatics analyses.
RESULTS
We found that patients with TNBC with high immune-infiltration treated with capecitabine were more likely to have a better prognosis. We used a cutoff of ≥25 combined positive score (CPS) of PD-L1, ≥10% positive sTILs, and ≥10% positive cells of CD8 to define the "immune-hot" patients. Among immune-hot patients, Kaplan-Meier curves showed that 5-year DFS rates were 96.9% and 79.4% in the capecitabine and control groups, respectively (hazard ratio, 0.13; 95% CI, 0.03-0.52; P=.049 in favor of capecitabine). In the capecitabine group, the 5-year DFS rate was higher for immune-hot patients than for immune-cold patients (96.9% vs 76.4%; hazard ratio, 0.11; 95% CI, 0.04-0.29; P=.028).
CONCLUSIONS
Our study suggested that immune-hot patients with TNBC are more likely to benefit from adjuvant capecitabine, and that combining immunotherapy with chemotherapy may be expected to be more effective in immune-hot patients.
论文信息
- 作者
- Wu W、Yang Y、Yang W、Pang D、Liu Y、Sheng Y、Li X、Yu S
- 单位
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.China
- 文献类型
- 多中心研究 · III 期临床试验
- 期刊
- Journal of the National Comprehensive Cancer Network : JNCCN2024 Oct
- 原文标识
- PubMed 39413834 · DOI 10.6004/jnccn.2024.7032