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:Evaluation of triple negative breast cancer with heterogeneous immune infiltration.
Evaluation of triple negative breast cancer with heterogeneous immune infiltration.
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这凸显了肿瘤内异质性驱动免疫浸润的重要性,而非患者特征如 HLA 表型、胚系 DNA 或免疫组库。
TIL(肿瘤浸润淋巴细胞)(TILs)已知是乳腺癌的预后和预测生物标志物,尤其是在三阴性乳腺癌(TNBC)患者中。国际指南已提出在临床环境中将其作为连续变量进行评估,而没有明确界定的截断值。然而,在某些情况下,免疫浸润具有异质性,即患者肿瘤的某些区域有大量TILs,而其他区域则完全缺乏。这种异质性免疫浸润的自发表现可能是一个绝佳的机会,用以研究为什么有些肿瘤在诊断时存在TILs而其他肿瘤则没有,同时消除患者间的差异。
在本研究中,我们确定了五名TNBC患者,其手术标本中显示出显著的TIL异质性,TIL数量存在低(5%)和高(50%)区域。为了评估免疫浸润异质性,我们对每位患者高TIL和低TIL区域的三个独立三重样本进行了批量RNA测序并分析。
在每个区域的三个重复样本中基因表达是同质的,但在TILs区域之间则显著不同。这些差异不仅仅是因为TILs的存在,因为在这两个区域之间还有其他非炎症基因和通路存在差异表达。
In this study, we have identified five TNBC patients that showed great TIL heterogeneity, with areas of low ( 5%) and high ( 50%) numbers of TILs in their surgical specimens. To evaluate immune infiltration heterogeneity, we performed and analyzed bulk RNA-sequencing in three independent triplicates from the high and low TIL areas of each patient.
Gene expression was homogeneous within the triplicates in each area but was remarkable different between TILs regions. These differences were not only due to the presence of TILs as there were other non-inflammatory genes and pathways differentially expressed between the two areas. DISCUSSION: This highlights the importance of intratumour heterogeneity driving the immune infiltration, and not patient's characteristics like the HLA phenotype, germline DNA or immune repertoire.
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