诱导的B细胞受体多样性预测PD-1阻断免疫疗法反应
Yonglu Che1, Jinwoo Lee1, Farah Abou-Taleb1
1Department of Dermatology, Stanford University School of Medicine, Redwood City, CA, USA.
bioRxiv : the preprint server for biology
|December 16, 2024
概括
抗PD-1疗法后增加的B细胞受体多样性预测了癌症治疗的成功. 这种多样性增强T细胞激活和瘤清除,作为各种癌症的可概括的预后标志物.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 基因组学就是基因组学.
背景情况:
- 免疫检查点抑制剂,如抗PD-1抗体 (aPD1),在晚期癌症中表现出有效性.
- 患者对aPD1治疗的反应有所不同,不完全理解非反应的机制.
研究的目的:
- 研究B细胞受体 (BCR) 多样性对aPD1治疗的反应中的作用.
- 为了确定对aPD1治疗的反应和不反应的预测因素.
主要方法:
- 在瘤和淋巴结上单细胞RNA测序和空间转录组学.
- 空间免疫受体分析和长期临床随访.
- 机器学习模型开发用于从基线RNA测序预测BCR多样性.
主要成果:
- 成功的aPD1反应与治疗后诱导的BCR克隆多样性相关.
- 诱导的BCR克隆与T细胞共定位并激活T细胞,有助于瘤清除.
- BCR多样性预测了基底细胞癌,质母细胞瘤,黑色素瘤以及头癌的反应.
- 一个基因表达特征预测BCR多样性诱导,使机器学习模型能够进行预测.
结论:
- BCR多样性是免疫治疗反应的动态因素.
- BCR多样性作为aPD1治疗的可概括的预后标志物.
- 针对B细胞多样性的向可能会改善非响应者的结果.
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