酸盐在瘤微环境中影响瘤生长,并调节与瘤相关的巨细胞
Sahil Inamdar1, Abhirami P Suresh2, Joslyn L Mangal2
1Chemical Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85281, USA.
Biomaterials
|August 29, 2023
概括
聚乙烯酸盐 (PES) 微粒将酸盐输送到瘤微环境中,增强抗癌免疫反应. 这种方法减少了瘤体积,并促进了亲炎性免疫细胞,这表明了一种新的癌症免疫治疗策略.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 生物材料科学 生物材料科学
背景情况:
- 酸盐是影响瘤微环境 (TME) 内免疫和癌细胞功能的关键代谢物.
- 调节免疫代谢对开发有效的癌症疗法充满希望.
研究的目的:
- 调查聚乙烯酸盐 (PES) 微粒 (MP) 在TME中控制酸盐输送的潜力.
- 在黑色素瘤模型中评估PES MPs对巨细胞反应和抗瘤免疫力的影响.
主要方法:
- 在免疫缺陷小鼠携带BRAF突变黑色素瘤中,局部使用PES MPs,带有或没有BRAF抑制剂.
- 在TME中分析瘤体积,巨细胞两极分化 (M1) 和免疫细胞群 (T助手类型1和17).
- 评估分子通路,包括TSLP和1型干扰素信号.
主要成果:
- 当地交付的PES国会议员显著减少了黑色素瘤瘤体积的三倍.
- 欧洲社会党议员促进了M1巨细胞两极分化,并提高了TSLP和1型干扰素通路的调节.
- 治疗诱导了亲炎性自适应性免疫反应,其特征是T辅助型1和T辅助型17细胞的增加.
结论:
- 修改免疫代谢的PES MP策略代表了癌症免疫治疗的有希望的方法.
- 通过PES MPs进行受控的酸递送可以调节TME以增强抗瘤免疫力.
- 这一策略显示出治疗具有挑战性的瘤模型的潜力,包括BRAF突变黑色素瘤.
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