从非结合性和自身反应性的前体进化出瘤反应性抗体
Roei D Mazor1, Nachum Nathan2, Amit Gilboa3
1Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel.
Cell
|March 19, 2022
概括
卵巢癌中的抗体分泌细胞 (ASC) 产生瘤向抗体. 身体突变 (SHM) 驱动抗体对表面自身抗原的反应性,为癌症诊断和治疗提供了潜力.
科学领域:
- 免疫学
- 癌症学
- 分子生物学
背景情况:
- 瘤微环境中的抗体分泌细胞 (ASC) 与各种癌症的更好的预后相关.
- 抗体获得瘤向 (自主活性) 能力的机制在很大程度上是未知的.
- 在癌症诊断和治疗方面,
研究的目的:
- 研究体质突变 (SHM) 在产生抗瘤抗体活性中的作用.
- 确定针对高度卵巢癌 (HGSOC) 瘤的自身抗体的来源和特征.
- 探索瘤反应性自身抗体在癌症治疗中的潜力.
主要方法:
- 对HGSOC患者的内ASC进行分析.
- 对患者的瘤细胞进行IgG涂层的评估.
- 对ASC的突变和克隆扩张分析.
- 针对MMP14等表面自身抗原的瘤反应性抗体的表征.
- 将单克隆抗体恢复到它们的生殖基因结构.
主要成果:
- 在HGSOC中,患者获得的瘤细胞经常被IgG覆盖.
- 内ASC显示突变和克隆扩张,产生针对MMP14表面自身抗体的抗体.
- 确定了两种类型的抗体:需要SHM结合瘤的抗体和具有固有的生殖系自身反应的抗体.
- 这些发现表明,瘤反应性自身抗体可以通过抗原驱动的选择自然发生或演变.
结论:
- 身体突变是促进HGSOC抗体对表面自身抗原的关键机制.
- 瘤反应性自身抗体是通过自然或抗原驱动的进化过程产生的.
- 了解这些自身抗体的起源,可以了解它们在表面抗原向癌症治疗中的潜在应用.
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