基因改造的骨髓细胞在转移中重新平衡核心免疫抑制程序
Sabina Kaczanowska1, Daniel W Beury1, Vishaka Gopalan2
1Tumor Microenvironment and Metastasis Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Cell
|March 25, 2021
概括
在转移前的位中,通过提供IL-12的工程细胞准髓状细胞免疫抑制,可以减少瘤负担并改善小鼠的存活率. 这种方法可以重新平衡转移的微环境,
科学领域:
- 癌症学
- 免疫学
- 癌症转移
背景情况:
- 转移是癌症死亡的主要原因,需要更深入地了解转移前的位.
- 推动转移性进展的关键监管信号在这个利基领域仍然不明朗.
- 骨髓细胞被确定为在转移前位形成期间免疫抑制的关键调节者.
研究的目的:
- 识别和向前转移内的免疫抑制机制.
- 研究基因工程骨髓细胞 (GEMys) 的治疗潜力,这些细胞可以输送Interleukin-12 (IL-12) 来调节转移性微环境.
主要方法:
- 在转移前的基因特征中确定核心免疫抑制基因,主要由髓质细胞表达.
- 开发和利用转基因骨髓细胞 (GEMys) 来输送IL-12.
- 在临床前癌症模型中评估IL12- GEMy治疗对免疫细胞活性,瘤负担和生存的影响.
主要成果:
- 在转移前的位中,IL12- GEMy治疗有效地逆转了免疫抑制.
- 治疗导致抗原呈现和T细胞激活的增强.
- 转移性和原发性瘤负担的显著降低,以及瘤携带小鼠的生存率的改善.
结论:
- 提供IL-12的基因工程骨髓细胞可以功能性地调节前转移中的免疫抑制程序.
- 这种策略成功地平衡了转移性微环境的失调,
- 针对骨髓驱动的免疫抑制是对抗癌症转移的可行策略.
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