在癌和骨髓状细胞中调节HHLA2表达
Tomonari Shigemura1, Nahuel Perrot2, Zimo Huang2
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave., Boston, MA, 02215, USA.
BMC cancer
|October 27, 2023
概括
人体内源性逆转录病毒-H LTR-关联2 (HHLA2) 在癌中的表达受到瘤微环境的调节. 在体内信号会在瘤中诱导HHLA2,但在体外并非如此,这凸显了对治疗开发的进一步研究的需要.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 免疫检查点HHLA2 (HERV-H LTR-关联2) 在癌和其他瘤中存在.
- 针对HHLA2或KIR3DL3的治疗方法正在开发中,用于固体瘤,包括细胞癌 (RCC).
- 了解瘤和微环境中的HHLA2调节对于治疗成功至关重要.
研究的目的:
- 为了研究HHLA2表达在癌中的调节.
- 探索瘤微环境对HHLA2表达的影响.
- 了解瘤细胞与免疫细胞中的差异HHLA2调节.
主要方法:
- 流细胞计和qRT-PCR分析了HHLA2表达在初级脏瘤和细胞系 (A498,786-O).
- 研究了HHLA2表达在体外,体内 (NSG小鼠的异种移植) 和单细胞/树突细胞.
- 检测了细胞因子,缺氧和培养条件,以检测它们诱导HHLA2表达的能力.
主要成果:
- 在原发性脏瘤中,HHLA2被表达为ex vivo,但在体外减少.
- 在体外,A498和786-O细胞缺乏HHLA2,但在体内以异种移植的形式表达它.
- 细胞因子 (IL-10,BMP4,IL-1β,IL-6) 在单细胞/树突细胞中适度增加HHLA2,但在体外瘤细胞系中没有.
结论:
- 癌的HHLA2表达在体内是由瘤微环境信号诱导的,而在体外则没有.
- 在癌上皮细胞和单细胞中,HHLA2的调节方式不同.
- 在单细胞中诱导HHLA2的细胞因子不会在瘤细胞系中对其进行上调,强调瘤细胞与微环境的相互作用.
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