对内源逆转录病毒的抗体促进肺癌免疫治疗
Kevin W Ng1, Jesse Boumelha2, Katey S S Enfield3
1Retroviral Immunology Laboratory, The Francis Crick Institute, London, UK.
Nature
|April 12, 2023
概括
肺癌中的三级淋巴体结构 (TLS) 与更好的免疫治疗反应相关. 内源逆转录病毒 (ERV) 抗体,通过免疫疗法强化,驱动抗瘤活性,需要TLS才能有效.
科学领域:
- 免疫学
- 癌症学
- 癌症研究
背景情况:
- 在固体瘤中发现的三级淋巴体结构 (TLS) 与患者的存活率和免疫检查点阻塞 (ICB) 反应的改善相关.
- 连接TLS与免疫治疗反应的机制尚不清楚.
- 肺腺癌在TLS中表现出B细胞反应.
研究的目的:
- 研究B细胞反应在肺癌中的作用及其与三级淋巴细胞结构 (TLS) 和免疫治疗的关联.
- 在肺腺癌中确定抗瘤抗体的特定点.
- 阐明TLS影响免疫疗法的机制.
主要方法:
- 对肺癌患者队列的分析 (TRACERx 421) 和免疫性小鼠模型.
- 使用瘤结合测定方法识别抗体点.
- 对B细胞反应,TLS形成和抗瘤活性进行评估.
- 免疫疗法 (ICB) 和向KRAS (G12C) 抑制效应的评估.
主要成果:
- 肺腺癌诱导生殖中心反应和瘤结合抗体,其中内源性逆转录病毒 (ERV) 包膜糖蛋白是主要点.
- 通过ICB和KRAS (G12C) 抑制,针对ERV的B细胞反应得到增强.
- 在小鼠中,ERV反应性抗体表现出抗瘤活性并改善生存率.
- 在人类肺腺癌中,ERV表达预测了ICB结果.
- 有效的免疫治疗需要依赖CXCL13的TLS形成,而CXCL13治疗可以增强抗瘤免疫力.
结论:
- 针对内源逆转录病毒 (ERV) 的B细胞反应对于肺腺癌的抗瘤活性至关重要.
- 由CXCL13驱动的三级淋巴细胞结构 (TLS) 形成对于有效的免疫治疗至关重要.
- 针对ERV特异性B细胞反应和促进TLS形成是肺癌的潜在治疗策略.
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