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靶向 LAIR1 介导的免疫抑制为免疫治疗武器库增添新武器

英文原题:Targeting LAIR1-mediated immunosuppression adds a new weapon to our immunotherapy arsenal.

查看英文原题

Targeting LAIR1-mediated immunosuppression adds a new weapon to our immunotherapy arsenal.

PubMed 2025/08/15(内容时间) J Clin Invest Q1 · IF 14.3(JCR 2025)

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中文摘要

白细胞相关免疫球蛋白样受体 1(LAIR1)是一种结合胶原的抑制性免疫受体,可负向调节细胞活化。本期 JCI 中,Tao 等人显示,在侵袭性脑肿瘤的免疫抑制性 M2 样肿瘤相关巨噬细胞(TAM)中,LAIR1 抑制信号发挥重要作用。LAIR1 基因敲除、抗体阻断,以及将 LAIR1 抑制模块整合进 CAR 的免疫疗法,均可提高 CAR-T 抗肿瘤活性、减少 M2 样 TAM、改变胶原网络,并提高小鼠肿瘤模型生存率。这些发现展示了一种创新癌症免疫治疗方法,通过抑制 LAIR1 对抗多种肿瘤免疫逃逸机制。

展开英文摘要原文

Leukocyte-associated Ig-like receptor 1 (LAIR1) is a collagen-binding inhibitory immune receptor that negatively regulates cellular activation. In this issue of the JCI, Tao et al. show that LAIR1-inhibitory signaling plays an important role in immunosuppressive M2-like tumor-associated macrophages (TAMs) in aggressive brain tumors.

LAIR1 KO, antibody blockade, and an immunotherapy that incorporates a LAIR1-inhibitory module into a chimeric antigen receptor (CAR) all led to increased antitumor activity by CAR T cells, reduced M2-like TAMs, altered collagen networks, and increased survival rates in mouse tumor models.

These findings demonstrate an innovative immunotherapeutic approach for cancer that leverages LAIR1 inhibition to combat multiple tumor immune evasion strategies.

论文信息

作者
Perrin EP、Dorando HK、Payton JE
文献类型
评论 · 非美国政府资助研究
期刊
The Journal of clinical investigation2025 Aug 15
原文标识
PubMed 40829176 · DOI 10.1172/JCI194924