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
英文原题:Dynamic Hybrid Module-Driven NK Cell Stimulation and Release for Tumor Immunotherapy.
Dynamic Hybrid Module-Driven NK Cell Stimulation and Release for Tumor Immunotherapy.
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自然杀伤(NK)细胞是过继肿瘤免疫治疗的强力候选,但治疗实体瘤的疗效仍不理想。本研究开发了一种由可注射水凝胶和羟基磷灰石(HAp)纳米带组成的混合模块,可控递送NK细胞以增强实体瘤治疗。表面功能化HAp纳米带修饰了针对NKG2D和4-1BB的激动性抗体,以及IL-2和IL-21细胞因子,可支持NK细胞存活并动态活化。因此,HAp修饰的壳聚糖(CS)热敏水凝胶不仅使NK细胞在体内滞留时间超过20天,还使NK细胞功能提高一倍以上。这种生物材料复合物的独特结构保护NK细胞免受肿瘤恶劣微环境影响并增强抗肿瘤效能。利用生物相容性水凝胶储库为NK细胞构建暂时性炎症生态位,可能成为预防可切除肿瘤癌症复发的转化途径。
Natural killer (NK) cells have become a powerful candidate for adoptive tumor immunotherapy, while their therapeutic efficacy in solid tumors remains unsatisfactory.
Here, we developed a hybrid module with an injectable hydrogel and hydroxyapatite (HAp) nanobelts for the controlled delivery of NK cells to enhance the therapy of solid tumors. Surface-functionalized HAp nanobelts modified with agonistic antibodies against NKG2D and 4-1BB and cytokines IL-2 and IL-21 support survival and dynamic activation.
Thus, the HAp-modified chitosan (CS) thermos-sensitive hydrogel not only improved the retention of NK cells for more than 20 days in vivo but also increased NK cell function by more than one-fold. The unique architecture of this biomaterial complex protects NK cells from the hostile tumor environment and improves antitumor efficacy. The generation of a transient inflammatory niche for NK cells through a biocompatible hydrogel reservoir may be a conversion pathway to prevent cancer recurrence of resectable tumors.
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