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
NK 细胞通过 CCR5 大量聚集并交叉招募细胞毒性 T 细胞
英文原题：Natural killer cells swarm and cross-recruit cytotoxic T cells via CCR5.
查看英文原题
Natural killer cells swarm and cross-recruit cytotoxic T cells via CCR5.
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中文摘要
自然杀伤（NK）细胞和细胞毒性T淋巴细胞（CTL）正被试验作为细胞免疫疗法的介导者，但这些细胞毒性淋巴细胞被招募到实体瘤中的机制尚不完全清楚。在此，我们结合实体瘤模型和定量成像来研究NK细胞与靶标相互作用和远端细胞毒性淋巴细胞之间的相互作用。我们发现，小鼠和人类NK细胞都通过分泌结合CCR5受体的扩散性趋化因子而群集到肿瘤靶标。此外，我们表明活化的NK细胞和CTL可以通过CCR5直接相互交叉招募。通过在体内采用多步骤过继转移方案，我们证明肿瘤反应性NK细胞促进随后转移的NK细胞和CTL的肿瘤浸润。总之，这些结果表明NK细胞可以通过同型趋化因子信号群集，并且NK细胞和CTL参与对靶标的直接异型交叉招募。
展开英文摘要原文
Natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) are being trialed as mediators of cellular immunotherapies, but the mechanisms by which these cytotoxic lymphocytes are recruited into solid tumors are incompletely understood.
Here, we employ a combination of solid tumor models and quantitative imaging to investigate the interplay between NK cells engaging targets and distal cytotoxic lymphocytes.
We find that both murine and human NK cells swarm to tumor targets via secretion of diffusive chemokines that bind the CCR5 receptor.
Moreover, we show that activated NK cells and CTLs can directly cross-recruit one another via CCR5. By employing multi-step adoptive transfer protocols in vivo, we demonstrate that tumor-reactive NK cells promote the tumor infiltration of subsequently transferred NK cells and CTLs.
Together, these results demonstrate that NK cells can swarm via homotypic chemokine signaling and that NK cells and CTLs engage in direct heterotypic cross-recruitment to targets.
论文信息
- 作者
- Cremasco J、Tay SS、Yang G、Huber A、Kempe D、Tang R、Colakoglu F、Newman PLH
- 第一作者单位
- The Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; EMBL Australia, Single Molecule Science node, School of Biomedical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.Australia
- 通讯作者单位
- The Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; EMBL Australia, Single Molecule Science node, School of Biomedical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia; St. Vincent's Healthcare Clinical Campus, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, Sydney, NSW 2052, Australia. Electronic address: m.biro@unsw.edu.au.Australia
- 期刊
- Cell reports2026 Jun 23
- 原文标识
- PubMed 42217183 · DOI 10.1016/j.celrep.2026.117415