在结直肠癌中,SDCBP调节瘤微环境,瘤进展和抗PD1功效
Jiahua Yu1, Shijun Yu1, Jin Bai1
1Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Cancer gene therapy
|March 30, 2024
概括
合成结合蛋白 (SDCBP) 驱动着结直肠癌的进展和抗编程细胞死亡1 (aPD1) 治疗的抵抗力. 用甲抑制SDCBP通过重编程瘤微环境来增强aPD1的疗效.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 分子生物学分子生物学
背景情况:
- 反编程细胞死亡1 (aPD1) 疗法在结直肠癌 (CRC) 中显示出有限的疗效.
- 合成结合蛋白 (SDCBP) 对于细胞功能至关重要,并与癌症进展有关.
- 高SDCBP表达与免疫治疗反应不佳和CRC患者无病生存率降低相关.
研究的目的:
- 调查SDCBP在结直肠癌进展,免疫治疗反应和瘤微环境 (TME) 中的作用.
- 为了评估抑制SDCBP的治疗潜力,结合aPD1治疗CRC.
主要方法:
- 研究了CRC患者的SDCBP表达及其与临床结果的相关性.
- 在小鼠异种移植和肝转移模型中利用shRNA和甲 (ZnPT) 抑制SDCBP.
- 在ZnPT治疗后,分析了TME的变化,包括巨细胞极化 (M1/M2).
- 采用共同培养系统来确认SDCBP对巨细胞再极化的影响.
主要成果:
- 高SDCBP表达与免疫疗法不响应和CRC中较差的无病生存率有关.
- 抑制SDCBP (shRNA或ZnPT) 减少了CRC细胞的增殖和转移.
- 联合SDCBP抑制和aPD1疗法在临床前模型中显著提高了治疗疗效.
- ZnPT治疗通过减少M2巨细胞和增加M1巨细胞来转移TME,促进M2到M1再极化.
结论:
- SDCBP促进结直肠癌的扩散,转移,以及对免疫治疗的抵抗力.
- 甲 (ZnPT) 是SDCBP的有效抑制剂.
- 将ZnPT与aPD1疗法结合使用具有改善结直肠癌治疗结果的巨大潜力.
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