Transcriptomics of Canine Inflammatory Mammary Cancer Treated with Empty Cowpea Mosaic Virus Implicates Neutrophils in Anti-Tumor Immunity.

Transcriptomics of Canine Inflammatory Mammary Cancer Treated with Empty Cowpea Mosaic Virus Implicates Neutrophils in Anti-Tumor Immunity.
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用空的牛豆镶嵌病毒治疗的犬炎性乳腺癌的转录组学暗示了抗肿瘤免疫中的中性粒细胞。

DOI:
10.3390/ijms241814034
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发表时间:
2023-09-13
影响因子:
5.6
通讯作者:
Peña L
Peña L
中科院分区:
生物学2区
文献类型:
--
作者:
Barreno L;Sevane N;Valdivia G;Alonso-Miguel D;Suarez-Redondo M;Alonso-Diez A;Fiering S;Beiss V;Steinmetz NF;Perez-Alenza MD;Peña L

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犬炎性乳腺癌(IMC)是一种高度侵袭性和致死性的癌症,可作为人类炎症性乳腺癌(IBC)的有价值的动物模型,两者都缺乏有效的治疗方法。使用空豇豆花叶病毒(eCPMV)纳米颗粒的肿瘤内免疫疗法(IT-IT)已经显示出有希望的结果,证明了肿瘤大小的减小、更长的存活率和生活质量的改善。本研究比较了接受eCPMV IT-IT和药物治疗(MT)与MT单独治疗的IMC雌性犬的肿瘤样本的转录组学特征。使用NanoString Technologies,使用犬免疫肿瘤学小组,评价了来自4只eCPMV治疗的IMC犬和4只MT治疗的IMC犬的样本中免疫细胞群的转录组学分析、基因表达谱、信号传导途径和细胞类型分析。比较分析显示,处理和未处理的样品之间的差异表达的基因34。参与嗜中性粒细胞募集和活化的五个基因(CXCL 8、S100 A9、CCL 20、IL 6和PTGS 2)在处理的样品中上调,与IL 17信号传导途径相关。细胞类型分析显示eCPMV治疗后肿瘤微环境中的中性粒细胞群体显著增加。这些发现强调了中性粒细胞在eCPMV IT-IT介导的抗肿瘤反应中的作用,并表明eCPMV是IBC/IMC的新治疗方法。
Canine inflammatory mammary cancer (IMC) is a highly aggressive and lethal cancer in dogs serving as a valuable animal model for its human counterpart, inflammatory breast cancer (IBC), both lacking effective therapies. Intratumoral immunotherapy (IT-IT) with empty cowpea mosaic virus (eCPMV) nanoparticles has shown promising results, demonstrating a reduction in tumor size, longer survival rates, and improved quality of life. This study compares the transcriptomic profiles of tumor samples from female dogs with IMC receiving eCPMV IT-IT and medical therapy (MT) versus MT alone. Transcriptomic analyses, gene expression profiles, signaling pathways, and cell type profiling of immune cell populations in samples from four eCPMV-treated dogs with IMC and four dogs with IMC treated with MT were evaluated using NanoString Technologies using a canine immune-oncology panel. Comparative analyses revealed 34 differentially expressed genes between treated and untreated samples. Five genes (CXCL8, S100A9, CCL20, IL6, and PTGS2) involved in neutrophil recruitment and activation were upregulated in the treated samples, linked to the IL17-signaling pathway. Cell type profiling showed a significant increase in neutrophil populations in the tumor microenvironment after eCPMV treatment. These findings highlight the role of neutrophils in the anti-tumor response mediated by eCPMV IT-IT and suggest eCPMV as a novel therapeutic approach for IBC/IMC.
DOI: 10.1371/journal.pone.0031524
发表时间: 2012
期刊: PloS one
影响因子: 3.7
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