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
IL-18 预激的 NK 细胞招募树突状细胞并增强 PD-1 阻断介导的肿瘤治疗
英文原题：IL-18-primed NK cells recruit dendritic cells and potentiate tumor therapy mediated by PD-1 blockade.
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IL-18-primed NK cells recruit dendritic cells and potentiate tumor therapy mediated by PD-1 blockade.
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中文摘要
癌症免疫治疗的成功取决于先天性与适应性免疫的有效协同。研究者此前报告，在小鼠模型中，IL-18 可增强免疫检查点抑制剂的治疗作用。
本研究显示，IL-18 预激活的自然杀伤（NK）细胞可将 I 型常规树突状细胞（cDC1）募集至肿瘤部位并促进 I 型免疫应答，从而增强抗 PD-1 抗体的抗肿瘤作用。IL-18 预激活 NK 细胞呈现未成熟表型，并表达参与 cDC1 募集的趋化因子。在 IL-18 联合抗 PD-1 抗体治疗中，清除 NK 细胞会抑制 cDC1 募集并消除治疗作用。
此外，过继转移 IL-18 预激活 NK 细胞可诱导 cDC1 募集并增强抗 PD-1 抗体疗效。IL-18 还提高树突状细胞中的 IL-12 mRNA 表达及血液 IL-12 水平；IL-12 则上调 NK 细胞中的 XCL1 表达。这些结果提示，IL-18 可预激活 NK 细胞，并通过促进树突状细胞参与的前馈环路增强免疫检查点抑制剂疗效。
展开英文摘要原文
The success of cancer immunotherapy depends on the effective coordination of innate and adaptive immunity.
We previously reported that IL-18 potentiates the therapeutic effects of immune checkpoint inhibitors in mouse models.
Here, we report that IL-18-primed natural killer (NK) cells enhanced the antitumor effects of anti-PD-1 antibodies by mobilizing type 1 conventional dendritic cells (cDC1s) to tumor sites and promoting type 1 immune responses. IL-18-primed NK cells had a premature phenotype, and expressed chemokines involved in cDC1 mobilization. In a combination treatment with IL-18 and anti-PD-1 antibody, NK cell depletion inhibited cDC1 mobilization and abrogated the therapeutic effects.
Additionally, adoptive transfer of IL-18-primed NK cells induced cDC1 mobilization and enhanced the therapeutic effects of anti-PD-1 antibodies. IL-18 also increased IL-12 mRNA expression in DCs and IL-12 blood levels, and IL-12 upregulated XCL1 expression in NK cells. These results suggest that IL-18 primes NK cells and enhances the therapeutic effects of immune checkpoint inhibitors by promoting a feed-forward loop involving DCs.
论文信息
- 作者
- Ohno Y、Okamura H、Yagita H、Tanaka T
- 单位
- Laboratory of Immunobiology, School of Pharmacy, Hyogo Medical University, Kobe, Hyogo, Japan.Japan
- 期刊
- Frontiers in oncology2025
- 原文标识
- PubMed 40165899 · DOI 10.3389/fonc.2025.1533808
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