CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
早期乳腺癌新辅助化疗反应与上皮-间质转化及 TIL（肿瘤浸润淋巴细胞）相关
英文原题：Response to neoadjuvant chemotherapy in early breast cancers is associated with epithelial-mesenchymal transition and tumor-infiltrating lymphocytes.
查看英文原题
Response to neoadjuvant chemotherapy in early breast cancers is associated with epithelial-mesenchymal transition and tumor-infiltrating lymphocytes.
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中文摘要
上皮-间质转化（EMT）和TIL（肿瘤浸润淋巴细胞）（TILs）在早期乳腺癌（BC）中发挥核心作用，并与化疗耐药、干性和侵袭相关。
本研究的目的有两个：（a）通过研究EMT和TILs的预测价值，我们旨在评估新辅助化疗（NAC）后获得缓解的机会；（b）评估BC患者在接受NAC后EMT和TILs的潜在变化。
我们使用bulk RNA测序和免疫荧光（IF）检测EMT标志物（E-cadherin和vimentin）及淋巴细胞标志物（CD3、CD8、FOXP3），分析了100例接受NAC治疗的早期BC患者的NAC前和NAC后肿瘤样本。对于每种BC分子亚型，我们在RNA和蛋白质水平上比较了缓解与未缓解肿瘤之间EMT和TILs的表达。对NAC后有残留病灶的患者进行了NAC前和NAC后样本的配对分析。NAC前和NAC后样本的RNA测序鉴定出未缓解（RCB-II/III）与缓解（RCB-0/I）肿瘤之间EMT相关和炎症相关基因表达的显著差异。在有残留病灶的病例中，NAC后观察到EMT相关标志物表达增加，尤其是在luminal亚型中。NAC前样本中TILs的表征显示，缓解的HER2+肿瘤中CD3 + CD8-FOXP3-淋巴细胞显著多于未缓解肿瘤。NAC前和NAC后样本的配对分析表明，残留luminal和三阴性BC中CD3 + CD8 + FOXP3-淋巴细胞水平较高，残留三阴性BC中CD3 + CD8-FOXP3-淋巴细胞水平高于其他亚型的淋巴细胞。
我们发现，临床上缺乏可靠的生物标志物来预测BC对NAC的应答，这一需求尚未得到满足。我们的结果提示，诊断性活检中EMT基因特征的上调与早期BC对所有亚型NAC应答不佳相关。
此外，NAC后残留肿瘤中发生了EMT和TIL群体的变化。这些发现可能有助于未来NAC和辅助治疗方案的个体化。
展开英文摘要原文
Epithelial-mesenchymal transition (EMT) and tumor-infiltrating lymphocytes (TILs) play a central role in early-stage breast cancer (BC) and are associated with chemoresistance, stemness, and invasion. The objective of this study was two fold: (a) by investigating the predictive value of EMT and TILs, we aimed to estimate the chance of achieving a response after neoadjuvant chemotherapy (NAC) and (b) to evaluate the potential changes of EMT and TILs in BC upon NAC. Using bulk RNA sequencing and immunofluorescence (IF) for EMT (E-cadherin and vimentin) and lymphocyte markers (CD3, CD8, FOXP3), we analyzed pre- and post-NAC tumor samples from 100 early-BC patients treated with NAC. For each BC molecular subtype, we compared the expression of EMT and TILs, at the RNA and protein level, between responding and non-responding tumors.
Paired analysis of pre- and post-NAC samples was performed for patients with residual disease after NAC. RNA sequencing of pre- and post-NAC samples identified significant differences in EMT-related and inflammation-related gene expression between non-responding (RCB-II/III) and responding (RCB-0/I) tumors. Increased EMT-related marker expression was observed after NAC in cases with residual disease, in particular in the luminal subtype.
Characterization of TILs in pre-NAC samples showed substantially more CD3 + CD8-FOXP3-lymphocytes in responding HER2+ tumors compared with non-responding. Paired analyses of pre- and post-NAC samples demonstrated higher levels of CD3 + CD8 + FOXP3-lymphocytes in residual luminal and triple-negative BC and higher levels of CD3 + CD8-FOXP3-lymphocytes in residual triple-negative BC compared with other subtypes of lymphocytes.
We found that there is an unmet clinical need for reliable biomarkers to predict response to NAC in BC.
Our results suggest that an upregulation of the EMT gene signature in diagnostic biopsies is associated with poor response to NAC in early BC, across all subtypes.
Additionally, changes in EMT and in the TIL population occur in residual tumors after NAC.
These findings could help to personalize future NAC and adjuvant treatment regimens.
论文信息
- 作者
- Derouane F、Ambroise J、van Marcke C、Van Bockstal M、Berlière M、Galant C、Dano H、Lougué M
- 第一作者单位
- Department of Medical Oncology, University Hospital Leuven, Belgium.Belgium
- 通讯作者单位
- Pole of Medical Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Brussels, Belgium.Belgium
- 文献类型
- 临床试验
- 期刊
- Molecular oncology2025 Aug
- 原文标识
- PubMed 39912409 · DOI 10.1002/1878-0261.13813
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