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.
过继性自然杀伤(NK)细胞疗法是治疗三阴性乳腺癌的一种有前景的策略,但其疗效往往受到瘤内持久性差以及在免疫抑制性肿瘤微环境中功能耗竭的限制。
英文原题:Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy and anti-EGFR antibodies.
我们的结果表明,细胞周期基因的高表达,结合冷免疫表型,可能预测TNBC对NAT的强烈耐药及其后的快速进展。
为寻找接受新辅助化疗和抗EGFR抗体(NAT)治疗的三阴性乳腺癌(TNBC)的转移复发生物标志物,我们使用MSK-IMPACT检测、基因芯片、Nanostring技术和H&E上的TIL评估,对肿瘤基因组、转录组和免疫特征进行了评价。6例患者出现了快速致命性复发(RR),另外6例出现了较晚的非致命性复发(LR)。在NAT前,RR中6个MHC I类和13个MHC II类基因低表达,但富集于细胞周期相关通路中上调的基因。RR中NAT前的TIL数量非常低(<5%),且治疗后未增加。在NAT后残留肿瘤中,RR病例显示SOX2和CXCR4高表达。我们的结果表明,细胞周期基因高表达,结合冷免疫表型,可能预测TNBC对NAT的强耐药及其后的快速进展。这种生物标志物组合值得在更大规模的研究中验证。
To find metastatic recurrence biomarkers of triple-negative breast cancer (TNBC) treated by neoadjuvant chemotherapy and anti-EGFR antibodies (NAT), we evaluated tumor genomic, transcriptomic, and immune features, using MSK-IMPACT assay, gene arrays, Nanostring technology, and TIL assessment on H&E. Six patients experienced a rapid fatal recurrence (RR) and other 6 had later non-fatal recurrences (LR). Before NAT, RR had low expression of 6 MHC class I and 13 MHC class II genes but were enriched in upregulated genes involved in the cell cycle-related pathways. Their TIL number before NAT in RR was very low (<5%) and did not increase after treatment. In post-NAT residual tumors, RR cases showed high expression of SOX2 and CXCR4. Our results indicate that high expression of cell cycle genes, combined with cold immunological phenotype, may predict strong TNBC resistance to NAT and rapid progression after it. This biomarker combination is worth validation in larger studies.
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