RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
靶向 CD49a 增强 NK 细胞功能和抗肿瘤免疫
英文原题：CD49a Targeting Enhances NK Cell Function and Antitumor Immunity.
查看英文原题
CD49a Targeting Enhances NK Cell Function and Antitumor Immunity.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
约70%接受免疫检查点阻断治疗的患者会出现治疗耐药，因此有必要寻找其他免疫治疗靶点。CD49a是一种表达于NK细胞和T细胞上的膜蛋白。本研究发现，在多种小鼠肿瘤模型中，肿瘤浸润NK细胞表面的CD49a高表达；与CD49a阴性的肿瘤浸润NK细胞相比，CD49a阳性细胞耗竭程度更高。此外，在多个小鼠肿瘤模型中，敲除CD49a或特异性敲除NK细胞中的CD49a可减缓肿瘤生长并延长生存期，这主要归因于NK细胞在抗肿瘤作用中发挥的关键作用。使用单克隆抗体阻断CD49a可抑制小鼠肿瘤进展；联合抗PD-L1治疗则进一步增强抗肿瘤疗效。本研究揭示了NK细胞CD49a这一免疫治疗靶点，并指出靶向CD49a疗法具有潜在临床应用价值。
展开英文摘要原文
Approximately 70% of patients receiving immune checkpoint blockade therapies develop treatment resistance.
Thus, there is a need for the identification of additional immunotherapeutic targets. CD49a is a membrane protein expressed on NK cells and T cells. In this study, we found that CD49a was highly expressed on the surface of tumor-infiltrating NK cells in various mouse tumor models and that CD49a+ tumor-infiltrating NK cells were more exhausted than CD49a- tumor-infiltrating NK cells.
Furthermore, CD49a or NK-specific CD49a deficiency slowed tumor growth and prolonged survival in several mouse tumor models, primarily through the essential role played by NK cells in antitumor activities. Blockade of CD49a using an mAb suppressed tumor development in mice, and combination treatment with anti-PD-L1 further enhanced antitumor efficacy.
Our research reveals CD49a on NK cells as an immunotherapeutic target and highlights the potential clinical applications of CD49a-targeted therapies.
论文信息
- 作者
- Zhang Y、Li Y、Zhang Z、Zheng X、Peng H、Tian Z、Sun R、Sun H
- 第一作者单位
- Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, Hefei National Research Center for Physical Sciences at the Microscale, School of Basic Medical Sciences, The Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, Hefei, China.China
- 通讯作者单位
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Cancer immunology research2025 Jan 9
- 原文标识
- PubMed 39570767 · DOI 10.1158/2326-6066.CIR-24-0124