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 94063.
概括
成功的抗编程死亡-1 (aPD-1) 治疗反应与增加的B细胞受体 (BCR) 多样性有关,这有助于瘤清除. 这种BCR多样性预测了多种癌症类型的治疗成功.
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,如抗编程死亡-1 (aPD-1) 抗体,提供先进的癌症治疗,但在许多患者中缺乏有效性.
- 驱动对aPD-1疗法的差异性反应的机制尚未完全理解.
研究的目的:
- 研究B细胞受体 (BCR) 多样性对aPD-1疗法的反应中的作用.
- 为了确定aPD-1治疗反应的预测因素.
主要方法:
- 单细胞RNA测序和空间转录组学用于接受aPD-1治疗的基底细胞癌患者的瘤和淋巴结.
- 进行了空间免疫受体分析和长期临床随访.
- 机器学习模型被开发用于从基线瘤RNA测序预测BCR多样性.
主要成果:
- 成功的aPD-1治疗反应与诱导的B细胞受体 (BCR) 克隆多样性相关.
- 诱导的BCR克隆与T细胞克隆结合,增强了它们的激活,并促进了瘤清除.
- aPD-1诱导的BCR多样性预测了质母细胞瘤,黑色素瘤和头角状细胞癌队列的临床反应.
- 在治疗前瘤中的基因表达特征预测了BCR克隆多样性的诱导.
结论:
- 增加BCR多样性是aPD-1免疫治疗反应成功的一个关键特征.
- 在各种癌症类型中,BCR多样性作为一种可概括的预后标志物.
- 准B细胞多样性可以提高免疫疗法在不响应者中的疗效.
更多相关视频
10:18Author Spotlight: Magnetic Fluorescent Bead-Based Dual-Reporter Flow Analysis of PDL1-Vaxx Peptide Vaccine-Induced Antibody Blockade of the PD-1/PD-L1 Interaction
Published on: July 7, 2023
1.1K
09:26In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
14.0K
相关概念视频
Diversity of Antigen Receptors
393
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
393
B Cell Activation and Differentiation
1.3K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
1.3K
T Cell Activation and Clonal Selection
550
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
550
