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针对SIGLEC15作为一种新兴的免疫疗法,用于治疗形甲状腺癌

Lisha Bao¹, Ying Li², Xiaoping Hu³

¹Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, 310014, Hangzhou, China.

International immunopharmacology

|April 23, 2024

概括

无塑性甲状腺癌 (ATC) 是具有侵略性的,但向SIGLEC15显示出有前途. 阻断SIGLEC15可增强T细胞活性并抑制瘤生长,为ATC提供一种新的免疫治疗方法.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

无塑性甲状腺癌 (ATC) 是一种高度侵袭性的甲状腺癌,治疗选择有限.
针对PD-1/PD-L1的现有免疫疗法在ATC中表现出有限的疗效,原因是药物可用免疫检查点的限制.
酸结合性Ig类讲蛋白 (Siglecs) 代表了ATC新型免疫治疗策略的潜在领域.

研究的目的:

为了研究Siglecs在厌塑性甲状腺癌中的抗瘤潜力.
确定特定的Siglec家族成员在ATC中过度表达,并评估它们在瘤进展和免疫逃避中的作用.

主要方法:

微阵列数据集 (216个甲状腺癌组织) 和单细胞RNA测序的综合分析,以选Siglec表达.
描述SIGLEC15高ATC细胞及其与瘤微环境的相互作用.
在体外和体内实验中,在共同培养模型,斑马鱼外移植和免疫能力强的小鼠ATC模型中使用抗SIGLEC15抗体治疗.

主要成果:

SIGLEC15在ATC显著过度表达,特别是在癌细胞上,并与PRSS23和CD44表达相关.
高SIGLEC15的ATC细胞通过免疫抑制信号 (MIF-TNFRSF14,CXCL12-CXCR4) 与瘤微环境细胞 (包括T细胞) 的相互作用增加.
抗SIGLEC15抗体治疗增强了CD8+ T细胞细胞毒性,抑制了瘤生长,在小鼠中延长了生存时间,并调节了免疫细胞群 (M1/M2,NK,CD8+ T细胞增加;MDSCs减少).

结论:

SIGLEC15是对形甲状腺癌免疫疗法的有前途的治疗标.
阻断SIGLEC15可以通过增强T细胞激活和效应器功能来克服免疫抑制.
准SIGLEC15代表了一种新的策略,以改善ATC患者的治疗结果.

关键词:

无塑性甲状腺癌是一种无塑性甲状腺癌.免疫治疗是一种免疫疗法.在SIGLEC15中,有15个字母.瘤微环境是一个微环境.一个单细胞RNA测序的序列.

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