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:Comparison of PD-L1 (22C3) Expression in Paired Primary and Metastatic Breast Carcinoma.
Comparison of PD-L1 (22C3) Expression in Paired Primary and Metastatic Breast Carcinoma.
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我们的研究显示,在乳腺癌进展过程中,PD-L1 表达下降且分子特征不连贯。如果原发肿瘤为阴性,在某些特定的转移部位可考虑重复进行 PD-L1 IHC 检测。需要进一步研究以确定乳腺癌患者免疫检查点抑制剂(ICI)治疗的其他预测因素。
PD-L1免疫组织化学(IHC)正被用作包括乳腺癌在内的多种癌症类型中免疫治疗获益的预测标志物。然而,关于PD-L1状态的预后和预测价值及其与乳腺癌进展过程中分子特征相关性的认识仍然有限。
我们对33例乳腺癌患者的治疗前原发灶和转移灶切片进行了PD-L1(22C3)检测,这些患者均匹配了新辅助化疗后(p-NACT)样本。采用3种评分方法评估PD-L1表达:以1%为截断值的免疫细胞(IC)和肿瘤细胞(TC),以及以1为截断值的联合阳性评分(CPS)。来自11例患者的22份样本具有可用于分析的成功的基于荧光原位杂交(FISH)的分子数据。
在33例治疗前原发肿瘤中,PD-L1 IC、TC和CPS与间质TIL(肿瘤浸润淋巴细胞)(sTIL)、组织学分级3级及三阴性乳腺癌(TNBC)呈正相关。在配对的转移性肿瘤中,仅PD-L1 IC与sTIL呈正相关。原发肿瘤在IC和CPS方面显示比配对的转移性肿瘤更高的PD-L1表达。在来自肺、胸膜和肝脏的转移性肿瘤中发现了CPS由阴性向阳性的转换。与新辅助化疗前肿瘤相比,新辅助化疗后肿瘤也显示出PD-L1表达较低的趋势。6例患者有配对样本可用于分子和PD-L1比较,且其中无一例在原发肿瘤、新辅助化疗后肿瘤和转移性肿瘤之间显示一致的基因改变或PD-L1表达。
We performed an PD-L1 (22C3) assay in pre-treatment primary and metastatic tumor sections from 33 patients with breast carcinoma, matched for post neoadjuvant chemotherapy (p-NACT). PD-L1 expression was evaluated using 3 scoring methods: immune cell (IC) and tumor cell (TC) with a 1% as the cutoff value, and combined positive scores (CPS) with a 1 as the cutoff value. Twenty-two samples from 11 patients had successful fluorescence in situ hybridization (FISH)-based molecular data available for analysis.
In the 33 pre-treatment primary tumors, PD-L1 IC, TC, and CPS showed positive correlation with stromal tumor infiltrate lymphocytes (sTIL), histological grade 3, and triple negative breast carcinoma (TNBC). In the matched metastatic tumors, only PD-L1 IC showed a positive correlation with sTIL. The primary tumors showed a higher PD-L1 expression than the matched metastatic tumors by IC and CPS. Negative to positive conversion by CPS was identified in the metastatic tumors from lung, pleura and liver. p-NACT tumors also showed a trend of lower PD-L1 expression compared to the pre-treatment tumors. Six patients had matched samples for molecular and PD-L1 comparison, and none of them showed consistent gene alterations or PD-L1 expression among the primary, p-NACT and metastatic tumors.
Our study showed a decrease in PD-L1 expression and disconnected molecular features during breast cancer progression. Repeating PD-L1 IHC testing could be considered in some specific metastatic sites if primary tumors were negative. Further studies are needed to identify other predictive factors for immune checkpoint inhibitor (ICI) therapy in patients with breast carcinoma.
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