紧张是淋巴瘤中一个关键的抑制检查点受体
James Godfrey1, Xiufen Chen2, Nicole Sunseri2
1Hematology, City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Journal for immunotherapy of cancer
|June 26, 2023
概括
结合PD-1和TIGIT检查点阻塞疗法显示出治疗扩散性大B细胞淋巴瘤 (DLBCL) 的前景. 这种组合疗法导致大多数淋巴瘤小鼠的瘤完全排斥,提供了一种新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症研究 癌症研究
背景情况:
- PD-1检查点阻塞疗法 (CBT) 在扩散大B细胞淋巴瘤 (DLBCL) 中显示出有限的疗效.
- 基于T细胞免疫球蛋白和免疫受体氨酸的抑制动机域 (TIGIT) 是一种涉及T细胞功能障碍的共抑制受体.
- 在DLBCL中T细胞功能障碍中TIGIT的作用需要进一步探索.
研究的目的:
- 研究DLBCL中TIGIT的表达和功能.
- 在DLBCL模型中评估联合PD-1和TIGIT阻塞的疗效.
主要方法:
- 在人类和小鼠淋巴瘤中对淋巴瘤透T细胞 (LIT) 的TIGIT和PD-1表达的分析.
- 在ex vivo复兴后评估TIGIT+/PD-1+LITs的细胞因子产量.
- 在A20 B细胞淋巴瘤小鼠模型中对PD-1和TIGIT单疗法与组合疗法的评估.
主要成果:
- TIGIT在人类淋巴瘤的LIT中得到广泛表达,包括DLBCL,通常与PD-1共同表达.
- 来自DLBCL和小鼠淋巴瘤的TIGIT+/PD-1+LIT显示出细胞因子生产减少.
- 结合PD-1和TIGIT阻塞导致A20淋巴瘤的完全排斥,并延长小鼠的存活时间,超过单一治疗.
结论:
- TIGIT是DLBCL的一个相关标,在功能失调的T细胞上经常与PD-1共同表达.
- 结合PD-1和TIGIT阻塞在临床前模型中显示出显著的抗淋巴瘤活性.
- 这些发现支持对TIGIT和PD-1阻断治疗淋巴瘤的临床研究,包括DLBCL.
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