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:Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer.
Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer.
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在未接受辅助或新辅助化疗的早期 TNBC 患者中,TIL 水平较高的乳腺癌组织与显著更好的生存相关。这些结果提示,乳腺组织 TIL 丰度是早期 TNBC 患者的预后因素。
在未接受辅助或新辅助化疗的早期三阴性乳腺癌(TNBC)患者中,乳腺癌组织中TIL(肿瘤浸润淋巴细胞)丰度与癌症复发和死亡之间的关联尚不明确。
研究乳腺癌组织中TIL丰度与接受局部区域治疗但未接受化疗的早期TNBC患者生存率之间的关联。设计、设置、
对来自北美(明尼苏达州罗切斯特;加拿大不列颠哥伦比亚省温哥华)、欧洲(法国巴黎、里昂和维勒瑞夫;荷兰阿姆斯特丹和鹿特丹;意大利米兰、帕多瓦和热那亚;瑞典哥德堡)和亚洲(日本东京;韩国首尔)13个参与中心的个体患者水平数据进行的回顾性汇总分析,纳入1966名在1979年至2017年间诊断为TNBC的参与者(随访至2021年9月27日),这些参与者接受了手术治疗并接受或不接受放疗,但未接受辅助或新辅助化疗。对切除的原发肿瘤乳腺组织中的TIL丰度进行评估。主要结局为浸润性无病生存期[iDFS]。次要结局为无复发生存期[RFS]、无远处复发生存期[远处RFS,DRFS]和总生存期。使用按参与中心分层的多变量Cox模型评估相关性。
本研究纳入1966例TNBC患者(中位年龄56岁[IQR,39-71];55%为I期TNBC)。中位TIL水平为15%(IQR,5%-40%)。417例(21%)TIL水平为50%或以上(中位年龄41岁[IQR,36-63]),1300例(66%)TIL水平低于30%(中位年龄59岁[IQR,41-72])。I期TNBC中,TIL水平为50%或以上患者的5年DRFS为94%(95% CI,91%-96%),而TIL水平低于30%的患者为78%(95% CI,75%-80%);TIL水平为50%或以上患者的5年总生存率为95%(95% CI,92%-97%),而TIL水平低于30%的患者为82%(95% CI,79%-84%)。在中位随访18年时,校正年龄、肿瘤大小、淋巴结状态、组织学分级和是否接受放疗后,TIL每增加10%均与iDFS改善独立相关(风险比[HR],0.92 [0.89-0.94])、RFS(HR,0.90 [0.87-0.92])、DRFS(HR,0.87 [0.84-0.90])和总生存率(0.88 [0.85-0.91])相关(似然比检验,P < 10e-6)。
The association of tumor-infiltrating lymphocyte (TIL) abundance in breast cancer tissue with cancer recurrence and death in patients with early-stage triple-negative breast cancer (TNBC) who are not treated with adjuvant or neoadjuvant chemotherapy is unclear.
To study the association of TIL abundance in breast cancer tissue with survival among patients with early-stage TNBC who were treated with locoregional therapy but no chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: Retrospective pooled analysis of individual patient-level data from 13 participating centers in North America (Rochester, Minnesota; Vancouver, British Columbia, Canada), Europe (Paris, Lyon, and Villejuif, France; Amsterdam and Rotterdam, the Netherlands; Milan, Padova, and Genova, Italy; Gothenburg, Sweden), and Asia (Tokyo, Japan; Seoul, Korea), including 1966 participants diagnosed with TNBC between 1979 and 2017 (with follow-up until September 27, 2021) who received treatment with surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy. EXPOSURE: TIL abundance in breast tissue from resected primary tumors. MAIN OUTCOMES AND MEASURES: The primary outcome was invasive disease-free survival [iDFS]. Secondary outcomes were recurrence-free survival [RFS], survival free of distant recurrence [distant RFS, DRFS], and overall survival. Associations were assessed using a multivariable Cox model stratified by participating center.
This study included 1966 patients with TNBC (median age, 56 years [IQR, 39-71]; 55% had stage I TNBC). The median TIL level was 15% (IQR, 5%-40%). Four-hundred seventeen (21%) had a TIL level of 50% or more (median age, 41 years [IQR, 36-63]), and 1300 (66%) had a TIL level of less than 30% (median age, 59 years [IQR, 41-72]). Five-year DRFS for stage I TNBC was 94% (95% CI, 91%-96%) for patients with a TIL level of 50% or more, compared with 78% (95% CI, 75%-80%) for those with a TIL level of less than 30%; 5-year overall survival was 95% (95% CI, 92%-97%) for patients with a TIL level of 50% or more, compared with 82% (95% CI, 79%-84%) for those with a TIL level of less than 30%. At a median follow-up of 18 years, and after adjusting for age, tumor size, nodal status, histological grade, and receipt of radiotherapy, each 10% higher TIL increment was associated independently with improved iDFS (hazard ratio [HR], 0.92 [0.89-0.94]), RFS (HR, 0.90 [0.87-0.92]), DRFS (HR, 0.87 [0.84-0.90]), and overall survival (0.88 [0.85-0.91]) (likelihood ratio test, P < 10e-6).
In patients with early-stage TNBC who did not undergo adjuvant or neoadjuvant chemotherapy, breast cancer tissue with a higher abundance of TIL levels was associated with significantly better survival. These results suggest that breast tissue TIL abundance is a prognostic factor for patients with early-stage TNBC.
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