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通过树突细胞重编程恢复瘤免疫性

Olga Zimmermannova^1,2, Alexandra G Ferreira^1,2,3,4, Ervin Ascic^1,2

¹Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.

Science immunology

|July 7, 2023

概括

将癌细胞重新编程成抗原呈现细胞 (瘤APC) 可以增强免疫识别和抗瘤反应. 这种使用转录因子PU.1,IRF8和BATF3的新型免疫疗法方法,在延缓瘤生长和改善存活率方面表现有前途.

科学领域:

免疫学免疫学免疫学
癌症生物学癌症生物学
细胞重编程细胞重编程

背景情况:

癌细胞逃避免疫检测,部分原因是抗原呈现减少.
树突细胞对于启动针对瘤的适应性免疫反应至关重要.

研究的目的:

将癌细胞重新编程成专业的抗原呈现细胞 (瘤APC).
研究瘤APC在癌症免疫治疗中的治疗潜力.

主要方法:

利用了1型常规树突细胞 (cDC1) 的最小基因调节网络.
在36个癌细胞系中强制表达转录因子PU.1,IRF8和BATF3 (PIB).
在重编程瘤APC中评估了转录,表观遗传和功能变化.

主要成果:

重编程诱导cDC1表型,恢复抗原呈现复合体和共刺激分子.
瘤APC增强了MHC-I上的内源抗原呈现,激活了CD8+ T细胞.
重编程的细胞显示瘤发生能力受损,瘤生长延迟,活体生存率增加.
瘤APC与免疫检查点抑制剂显示出协同作用.

结论:

将癌细胞重新编程成瘤APC是一种可行的策略,可以增强抗瘤免疫力.
这种方法为开发针对内源性瘤抗原的新型免疫疗法提供了一个平台.
瘤APC可以从血液和固体瘤产生,包括人类初级细胞.

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