确定头癌患者的HPV特异性B细胞反应
Andreas Wieland1,2, Mihir R Patel3,4, Maria A Cardenas5
1Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. andreas.wieland@emory.edu.
Nature
|November 19, 2020
概括
在HPV阳性头瘤中发现人类乳头瘤病毒 (HPV) 特定的B细胞和抗体分泌细胞. 这些发现揭示了瘤微环境中的局部 humoral 免疫反应.
科学领域:
- 免疫学
- 癌症学
- 病毒学
背景情况:
- 瘤内B细胞和血细胞在瘤中很常见,但它们的抗原特异性尚不清楚.
- 了解瘤微环境中的B细胞反应对于癌症免疫学至关重要.
- 人类乳头瘤病毒 (HPV) 与头癌有关,这表明HPV特异性免疫反应可能起作用.
研究的目的:
- 在HPV阳性头癌中研究B细胞反应的抗原特异性.
- 在瘤微环境中描述HPV特异性B细胞和抗体分泌细胞的存在和功能.
- 探索瘤透B细胞的潜在治疗含义.
主要方法:
- 分析HPV阳性头癌患者的瘤样本.
- 通过各种免疫检测检测HPV特异性抗体和抗体分泌细胞 (ASC).
- 从内B细胞和血细胞生成和表征人类单克隆抗体.
- 单细胞RNA测序以识别瘤微环境中的B细胞群和它们的激活状态.
主要成果:
- 在瘤内检测到HPV特异性B细胞反应,包括HPV特异性IgG抗体的活跃产生.
- 在瘤微环境中鉴定出HPV特异性ASCs,并很少招募流感特异性细胞,表明局部反应.
- 针对HPV特定的ASC反应针对HPV蛋白质E2,E6和E7,对E2的反应占主导地位.
- 生成的HPV特异性单克隆抗体显示出高体质突变,表明长期暴露在抗原中.
- 单细胞RNA测序揭示了激活的B细胞,生殖中心B细胞和ASCs,它们优先定位在瘤层中,有持续生殖中心反应的证据.
结论:
- 抗原特异性B细胞,包括激活的生殖中心B细胞和血细胞,在HPV阳性头癌的瘤微环境中存在并具有功能.
- 这些发现有助于我们更好地了解癌症中的幽默免疫反应.
- 透瘤的B细胞是开发新型癌症疗法的潜在目标.
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