决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:A triple-negative breast cancer surrogate subtype classification that correlates with gene expression subtypes.
A triple-negative breast cancer surrogate subtype classification that correlates with gene expression subtypes.
我们开发了一种与 Vanderbilt 亚型相关的 TNBC 替代亚型分类。
背景:本研究基于Vanderbilt分型,开发了一种用于表示三阴性乳腺癌(TNBC)亚型的替代分型方法。 方法:纳入接受TNBC根治性手术的患者。采用代表性福尔马林固定石蜡包埋(FFPE)组织块进行基因表达分析,并构建组织芯片开展免疫组化(IHC)染色。将Vanderbilt亚型重新归为四组:基底样(BL)、间质样(M)、免疫调节型(IM)和管腔雄激素受体型(LAR)。研究采用分类与回归树(CART)模型建立替代分型。 结果:共纳入145例患者。按Vanderbilt四亚型分布为:LAR 22例(15.2%)、IM 32例(22.1%)、M 38例(26.2%)、BL 25例(17.2%),另有28例(19.3%)未分类。因9例(6.2%)IHC染色质量欠佳而排除后,进行CART建模。TNBC替代亚型定义如下:LAR型为雄激素受体Allred评分8分;IM型为LAR阴性且TIL(肿瘤浸润淋巴细胞)评分>70%;M型为LAR阴性且TIL评分<20%;BL型为LAR阴性、TIL评分20%至70%,并有弥漫强阳性p16染色。按替代亚型分布为:LAR 26例(17.9%)、IM 21例(14.5%)、M 44例(30.3%)、BL1 27例(18.6%),未分类18例(12.4%)。该替代分型预测Vanderbilt四亚型的准确率为0.708。 结论:本研究建立了一种与Vanderbilt亚型相关的TNBC替代分型。该检测实用、易获取,可方便地应用于临床。
BACKGROUND: This study developed a triple-negative breast cancer (TNBC) surrogate subtype classification that represents TNBC subtypes based on the Vanderbilt subtype classification. METHODS: Patients who underwent primary curative surgery for TNBC were included. Representative FFPE blocks were used for gene expression analysis and tissue microarray construction for immunohistochemical (IHC) staining. The Vanderbilt subtypes were re-classified into four groups: basal-like (BL), mesenchymal-like (M), immunomodulatory (IM) and luminal androgen receptor (LAR) subtype. Classification and regression tree (CART) modeling was applied to develop a surrogate subtype classification. RESULTS: A total of 145 patients were included. The study cohort was allocated to the Vanderbilt 4 subtypes as LAR (n = 22, 15.2%), IM (n = 32, 22.1%), M (n = 38, 26.2%), BL (n = 25, 17.2%) and unclassified (n = 28, 19.3%). After excluding nine (6.2%) patients due to poor IHC staining quality, CART modeling was performed. TNBC surrogate subtypes were defined as follows: LAR subtype, androgen receptor Allred score 8; IM subtype, LAR-negative with a tumor-infiltrating lymphocyte (TIL) score > 70%; M subtype, LAR-negative with a TIL score < 20%; BL subtype, LAR-negative with a TIL score 20-70% and diffuse, strong p16 staining. The study cohort was classified by the surrogate subtypes as LAR (n = 26, 17.9%), IM (n = 21, 14.5%), M (n = 44, 30.3%), BL1 (n = 27, 18.6%) and unclassified (n = 18, 12.4%). Surrogate subtypes predicted TNBC Vanderbilt 4 subtypes with an accuracy of 0.708. CONCLUSION: We have developed a TNBC surrogate subtype classification that correlates with the Vanderbilt subtype. It is a practical and accessible diagnostic test that can be easily applied in clinical practice.
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