将癌细胞重新编程为呈现抗原的细胞
Alexandra G Ferreira1,2,3,4, Olga Zimmermannova1,2, Ilia Kurochkin1,2
1Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden.
Bio-protocol
|November 29, 2023
概括
科学家使用特定的转录因子将癌细胞重新编程为抗原呈现细胞 (APC). 这种方法增强了T细胞对瘤的反应,为癌症疫苗和治疗提供了新的途径.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 癌细胞经常通过抑制抗原呈现来逃避免疫检测.
- 免疫检查点抑制剂和采用T细胞疗法具有前景,但依赖于瘤免疫性.
- 有效的癌症治疗需要瘤细胞和树突细胞强大的抗原呈现.
研究的目的:
- 开发一种直接将癌细胞重新编程成瘤抗原呈现细胞 (瘤APC) 的协议.
- 研究这些重编程瘤APC的表型,功能和治疗潜力.
主要方法:
- 使用cDC1转录因子 (PU.1,IRF8,BATF3) 的lentiviral输送,直接重新编程小鼠和人类癌细胞.
- 瘤APCs的特征使用流细胞测量用于细胞表面标记物 (CD45,MHC I/II,共刺激分子).
- 对T细胞的抗原呈现和体内抗瘤疗效的功能性评估.
主要成果:
- 重编程的瘤APC在9天内获得了cDC1类的表型和功能.
- 瘤APC有效地向CD8+和CD4+T细胞呈现抗原.
- 重编程的细胞在体内引起了抗瘤反应,并且被细胞毒性T淋巴细胞准.
结论:
- 直接重编程提供了一种强大的方法,通过增强抗原呈现来克服癌症免疫逃避.
- 这个平台有可能开发新的癌症疫苗,发现新抗原,并扩大瘤透性淋巴细胞.
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